Use of a polypeptide as neuroprotective agent
Specific artificial polypeptides are administered to subjects to address peripheral neuropathy and nerve injury, enhancing neuroprotection, neuroregeneration, and improving nerve function by promoting nerve conduction and increasing intraepidermal nerve fiber density.
Patent Information
- Application Number
- PCT/CN2025/082409
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-03-14
- Filing Date
- 2025-03-13
- Publication Date
- 2025-09-18
AI Technical Summary
There is an unmet need for effective treatments that can prevent and treat peripheral neuropathy and nerve injury, improve neuroprotection and neuroregeneration, alleviate cell damage and inflammatory responses, and enhance nerve conduction velocity and intraepidermal nerve fiber density in subjects affected by peripheral neuropathy.
Administration of specific artificial polypeptides, such as those with sequences having at least 70% identity to SEQ ID NOs 28, 57, and 62-74, or their variants, to subjects in need, to promote neuroprotection, neuroregeneration, and improve nerve function.
The polypeptides effectively prevent and treat peripheral neuropathy, enhance nerve conduction velocity, and increase intraepidermal nerve fiber density, while mitigating cell damage and inflammatory responses.
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Figure CN2025082409_18092025_PF_FP_ABST
Abstract
Description
USE OF A POLYPEPTIDE AS NEUROPROTECTIVE AGENTCROSS-REFERENCE
[0001] This application claims priority to the PCT application No. PCT / CN2024 / 081680 filed on March 14, 2024, the contents of which is herein incorporated by reference in its entirety.TECHNICAL FIELD
[0002] The present disclosure provides use of a polypeptide as neuroprotective agent. In particular, provided herein is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of any one of the polypeptides disclosed herein. BACKGROUNG
[0003] Peripheral neuropathy, often shortened to neuropathy, refers to a common type of conditions that involve damage to the peripheral nervous system, which is a vast communications network which sends signals between the central nervous system and all other parts of the body. Different types of neuropathies may cause different symptoms and affect different nerve functions. Neuropathy has a variety of causes, including underlying conditions such as autoimmune diseases, tumors, trauma, infections, metabolic problems, genetic causes, and exposure to toxins or medications such as chemotherapeutic agents or dietary supplements at high dose. For example, diabetic peripheral neuropathy (DPN) is a common complication of diabetes: more than half of the diabetic population will develop DPN during the course of the disease. Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of chemotherapy that limits the dose and potential effectiveness of many first-line agents used in cancer treatment.
[0004] Peripheral neuropathy is often accompanied by nerve injury, which can affect nerve cells, nerve fibers, nerve conduction, etc. Although the pathophysiology of peripheral nerve injury has been extensively studied, finding treatments that significantly improve post-injury neurogenesis, neurite formation, and neuroprotection has been a long-lasting elusive goal. Furthermore, despite the widespread prevalence of peripheral neuropathy, there still remains an unmet need in the medical community for drugs that effectively combat peripheral neuropathy or nerve injury associated therewith.SUMMARY
[0005] The present disclosure provides polypeptides for use in neuroprotection. Specifically, the present disclosure provides use of the polypeptides as neuroprotective agent, inter alia, a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof using any one of the polypeptides disclosed herein. More specifically, the present disclosure provides a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, improving nerve conduction velocity in a subject in need thereof, increasing intraepidermal nerve fiber density (IEFND) in a subject in need thereof, or any combination thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) , (II) , (III) , (IV) , (V) , (VI) , or (VII) , or a mutant of artificial polypeptide of (I) , (II) , (III) , (IV) or (V) , or a polypeptide having at least 70%identity with any one selected from SEQ ID NO. 28, SEQ ID NOs. 57 and 62-74 or a fragment or variant thereof ( “an artificial polypeptide of formula (I) , (II) , (III) , (IV) , (V) , (VI) , or (VII) , and a mutant of artificial polypeptide of (I) , (II) , (III) , (IV) or (V) , and a polypeptide having at least 70%identity with any one selected from SEQ ID NO. 28, SEQ ID NOs. 57 and 62-74 or a fragment or variant thereof” are sometimes collectively called “the polypeptides of the present disclosure” or “active ingredients” hereinafter) .
[0006] In one aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) : X-Y (I) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, and Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A; wherein Y comprises a total number of Cysteine (C) of less than 5.
[0007] In one aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) .
[0008] In one aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) .
[0009] In one aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) .
[0010] In one aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) .
[0011] In some embodiments, X comprises a sequence having at least 90%identity with SEQ ID NO: 1, X comprises a sequence having at least 95%identity with SEQ ID NO: 1, or X comprises a sequence of SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 95%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence of SEQ ID NO: 1. In some embodiments, at least 50%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 81-83.
[0012] In some embodiments, Y comprises a total number of Cysteine (C) of less than 4, Y comprises a total number of Cysteine (C) of less than 3, or Y comprises a total number of Cysteine (C) of less than 2. In some embodiments, Y comprises a total number of Cysteine (C) of less than 4. In some embodiments, Y comprises a total number of Cysteine (C) of less than 3. In some embodiments, Y comprises a total number of Cysteine (C) of less than 2. In some embodiments, a total number of hydrophobic amino acids in Y is more than 8, the total number of hydrophobic amino acids in Y is more than 12, the total number of hydrophobic amino acids in Y is more than 15, and / or a total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, a total number of hydrophobic amino acids in Y is more than 8. In some embodiments, the total number of hydrophobic amino acids in Y is more than 12. In some embodiments, the total number of hydrophobic amino acids in Y is more than 15. In some embodiments, a total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85, or Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85.
[0013] In some embodiments, the polypeptide comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 29-41, 54-57, 75 and 91-95.
[0014] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0015] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) : X-Y (II) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, and Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A; wherein Y comprises a sequence having at most 90%identity with SEQ ID NO: 2.
[0016] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) .
[0017] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) .
[0018] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) .
[0019] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) .
[0020] In some embodiments, X comprises a sequence having at least 90%identity with SEQ ID NO: 1, X comprises a sequence having at least 95%identity with SEQ ID NO: 1, or X comprises a sequence of SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 95%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence of SEQ ID NO: 1. In some embodiments, at least 50%amino acids of X are selected from R, K, N, D, Q, E, and H.
[0021] In some embodiments, Y comprises a sequence having at most 80%identity with SEQ ID NO: 2, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2, or Y comprises a sequence having at most 50%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 80%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 50%identity with SEQ ID NO: 2. In some embodiments, a total number of hydrophobic amino acids in Y is more than 8, the total number of hydrophobic amino acids in Y is more than 12, the total number of hydrophobic amino acids in Y is more than 15, and / or a total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, a total number of hydrophobic amino acids in Y is more than 8. In some embodiments, the total number of hydrophobic amino acids in Y is more than 12. In some embodiments, the total number of hydrophobic amino acids in Y is more than 15. In some embodiments, a total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 16-18, or Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 16-18.
[0022] In some embodiments, the polypeptide comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 42-44.
[0023] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0024] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) : X-Y (III) , wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; and Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2, wherein a total number of H, R, K, D, Q, N and E in X is less than 33.
[0025] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) .
[0026] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) .
[0027] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) .
[0028] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) .
[0029] In some embodiments, Y comprises a sequence having at least 90%identity with SEQ ID NO: 2, Y comprises a sequence having at least 95%identity with SEQ ID NO: 2, or Y comprises a sequence of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 90%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 95%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence of SEQ ID NO: 2. In some embodiments, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A.
[0030] In some embodiments, wherein the total number of H, R, K, D, Q, N and E in X is less than 30, the total number of H, R, K, D, Q, N and E in X is less than 25, or the total number of H, R, K, D, Q, N and E in X is less than 20. In some embodiments, the total number of H, R, K, D, Q, N and E in X is less than 30. In some embodiments, the total number of H, R, K, D, Q, N and E in X is less than 25. In some embodiments, the total number of H, R, K, D, Q, N and E in X is less than 20. In some embodiments, a total number of hydrophilic amino acids in X is more than 10, a total number of hydrophilic amino acids in X is more than 15, a total number of hydrophilic amino acids in X is more than 20, a total number of hydrophilic amino acids in X is more than 25, a total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10. In some embodiments, a total number of hydrophilic amino acids in X is more than 10. In some embodiments, a total number of hydrophilic amino acids in X is more than 15. In some embodiments, a total number of hydrophilic amino acids in X is more than 20. In some embodiments, a total number of hydrophilic amino acids in X is more than 25. In some embodiments, a total number of hydrophobic amino acids in X is no more than 15. In some embodiments, the total number of hydrophobic amino acids in X is no more than 10. In some embodiments, X comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 23-27, or X comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 23-27. In some embodiments, X comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 23-27. In some embodiments, X comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 23-27.
[0031] In some embodiments, the polypeptide comprises a sequence having at least 90%identity with SEQ ID NOs: 49-53.
[0032] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0033] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) : X-Y (IV) , wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; and Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2, wherein X comprises a sequence having at most 90%identity with SEQ ID NO: 1.
[0034] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) .
[0035] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) .
[0036] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) .
[0037] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) .
[0038] In some embodiments, X comprises a sequence having at most 80%identity with SEQ ID NO: 1, X comprises a sequence having at most 70%identity with SEQ ID NO: 1, or X comprises a sequence having at most 50%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at most 80%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at most 70%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at most 50%identity with SEQ ID NO: 1. In some embodiments, a total number of hydrophilic amino acids in X is more than 10, a total number of hydrophilic amino acids in X is more than 15, a total number of hydrophilic amino acids in X is more than 20, a total number of hydrophilic amino acids in X is more than 25, a total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10. In some embodiments, a total number of hydrophilic amino acids in X is more than 10. In some embodiments, a total number of hydrophilic amino acids in X is more than 15. In some embodiments, a total number of hydrophilic amino acids in X is more than 20. In some embodiments, a total number of hydrophilic amino acids in X is more than 25. In some embodiments, a total number of hydrophobic amino acids in X is no more than 15. In some embodiments, the total number of hydrophobic amino acids in X is no more than 10. In some embodiments, X comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 19-22 and 76-79, or X comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 19-22 and 76-79.
[0039] In some embodiments, Y comprises a sequence having at least 90%identity with SEQ ID NO: 2, Y comprises a sequence having at least 95%identity with SEQ ID NO: 2, or Y comprises a sequence of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 90%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 95%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence of SEQ ID NO: 2. In some embodiments, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A.
[0040] In some embodiments, the polypeptide comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 45-48 and 86-89.
[0041] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0042] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) : X-Y (V) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, and Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2.
[0043] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) .
[0044] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) .
[0045] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) .
[0046] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) .
[0047] In some embodiments, X comprises a sequence having at least 90%identity with SEQ ID NO: 1, X comprises a sequence having at least 95%identity with SEQ ID NO: 1, or X comprises a sequence of SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 95%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence of SEQ ID NO: 1. In some embodiments, at least 50%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 80%identity with SEQ ID NO: 96, X comprises a sequence having at least 90%identity with SEQ ID NO: 96, X comprises a sequence having at least 95%identity with SEQ ID NO: 96, or X comprises a sequence of SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 80%identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 90%identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 95%identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence of SEQ ID NO: 96.
[0048] In some embodiments, Y comprises 10 to 25 amino acids, Y comprises 10 to 20 amino acids, or Y comprises 10 to 15 amino acids. In some embodiments, Y comprises 10 to 25 amino acids. In some embodiments, Y comprises 10 to 20 amino acids. In some embodiments, Y comprises 10 to 15 amino acids.
[0049] In some embodiments, Y comprises a sequence having at most 80%identity with SEQ ID NO: 2, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2, or Y comprises a sequence having at most 50%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 80%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 50%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 97-103, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 97-103, Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 97-103, or Y comprises a sequence that is any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence that is any one selected from SEQ ID NOs: 97-103.
[0050] In some embodiments, the polypeptide comprises a sequence having at least 90%identity with any of SEQ ID NOs: 53-56 and 104-110.
[0051] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0052] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) : X-Y (VI) , wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in SEQ ID NO: 1 mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in SEQ ID NO: 1 mutated to T; and Y is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, or 5 C in SEQ ID NO: 2 mutated to A.
[0053] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) .
[0054] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) .
[0055] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) .
[0056] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) .
[0057] In some embodiments, X comprises a sequence having at least 70%identity with SEQ ID NO: 1 and / or X comprises a sequence having at most 95%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 70%identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at most 95%identity with SEQ ID NO: 1. In some embodiments, a total number of R, K, T, A, N, Q, D, E, S, and G in X is more than 30 and / or a total number of W, Y, F, M, L, I, and V in X is no more than 20. In some embodiments, a total number of R, K, T, A, N, Q, D, E, S, and G in X is more than 30. In some embodiments, a total number of W, Y, F, M, L, I, and V in X is no more than 20. In some embodiments, X comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 80-83, X comprises a sequence that is any one selected from SEQ ID NOs: 80-83, or X is a sequence that is any one selected from SEQ ID NOs: 80-83. In some embodiments, X comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 80-83. In some embodiments, X comprises a sequence that is any one selected from SEQ ID NOs: 80-83. In some embodiments, X is a sequence that is any one selected from SEQ ID NOs: 80-83.
[0058] In some embodiments, Y comprises a sequence having at least 80%identity with SEQ ID NO: 2 and / or Y comprises a sequence having at most 95%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 80%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 95%identity with SEQ ID NO: 2. In some embodiments, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, a total number of R, K, T, A, N, Q, D, E, S, and G in Y is more than 10 and / or a total number of W, Y, F, M, L, I, and V in Y is no more than 20. In some embodiments, a total number of R, K, T, A, N, Q, D, E, S, and G in Y is more than 10. In some embodiments, a total number of W, Y, F, M, L, I, and V in Y is no more than 20. In some embodiments, Y comprises a sequence having at least 80%identity with SEQ ID NO: 3, Y comprises a sequence of SEQ ID NO: 3, or Y is a sequence of SEQ ID NO: 3. In some embodiments, Y comprises a sequence having at least 80%identity with SEQ ID NO: 3. In some embodiments, Y comprises a sequence of SEQ ID NO: 3. In some embodiments, Y is a sequence of SEQ ID NO: 3.
[0059] In some embodiments, the artificial polypeptide comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 90-93, the artificial polypeptide comprises a sequence that is any one selected from SEQ ID NOs: 90-93, or the artificial polypeptide is a sequence that is any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide comprises a sequence that is any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide is a sequence that is any one selected from SEQ ID NOs: 90-93.
[0060] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0061] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) : X-Y (VII) , wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1, and Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 continuous AAs of SEQ ID NO: 2.
[0062] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) .
[0063] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) .
[0064] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) .
[0065] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) .
[0066] In some embodiments, the amino acid insertions are located at the N-terminal of X and / or the inserted amino acid is M. In some embodiments, the amino acid insertions are located at the N-terminal of X. In some embodiments, the inserted amino acid is M.
[0067] In some embodiments, at least 50%amino acids of X are selected from R, K, N, D, Q, E, and H and / or at most 60%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, a total number of E or D in X is at least 8 and / or a total number of E or D in X is at most 15. In some embodiments, a total number of E or D in X is at least 8. In some embodiments, a total number of E or D in X is at most 15. In some embodiments, a total number of R, K, T, A, N, Q, D, E, S, and G in X is more than 30 and / or a total number of W, Y, F, M, L, I, and V in X is no more than 20. In some embodiments, a total number of R, K, T, A, N, Q, D, E, S, and G in X is more than 30. In some embodiments, a total number of W, Y, F, M, L, I, and V in X is no more than 20. In some embodiments, X comprises a sequence having at least 80%identity with SEQ ID NO: 96, X comprises a sequence of SEQ ID NO: 96, or X is a sequence of SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 80%identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence of SEQ ID NO: 96. In some embodiments, X is a sequence of SEQ ID NO: 96.
[0068] In some embodiments, Y is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations relative to SEQ ID NO: 2 and optionally the at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations are located at the C-terminal of Y. In some embodiments, Y is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations relative to SEQ ID NO: 2. In some embodiments, the at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations are located at the C-terminal of Y. In some embodiments, Y comprises 15 to 25 amino acids, Y comprises 18 to 25 amino acids, or Y comprises 20 to 25 amino acids. In some embodiments, Y comprises 15 to 25 amino acids. In some embodiments, Y comprises 18 to 25 amino acids. In some embodiments, Y comprises 20 to 25 amino acids. In some embodiments, 40-65%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, a total number of R, K, T, A, N, Q, D, E, S, and G in Y is no more than 10 and / or a total number of W, Y, F, M, L, I, and V in Y is no more than 15. In some embodiments, a total number of R, K, T, A, N, Q, D, E, S, and G in Y is no more than 10. In some embodiments, a total number of W, Y, F, M, L, I, and V in Y is no more than 15. In some embodiments, Y comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 97-103, Y comprises a sequence that is any one selected from SEQ ID NOs: 97-103, or Y is a sequence that is any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence that is any one selected from SEQ ID NOs: 97-103. In some embodiments, Y is a sequence that is any one selected from SEQ ID NOs: 97-103.
[0069] In some embodiments, the artificial polypeptide comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 104-110, the artificial polypeptide comprises a sequence that is any one selected from SEQ ID NOs: 104-110, or the artificial polypeptide is a sequence that is any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide comprises a sequence that is any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide is a sequence that is any one selected from SEQ ID NOs: 104-110.
[0070] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0071] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) , X-Y (I) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A, Y comprises a total number of Cysteine (C) of less than 5, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.
[0072] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) .
[0073] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) .
[0074] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) .
[0075] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) .
[0076] In some embodiments, at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H, and / or at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70%identity with SEQ ID NO: 1.
[0077] In some embodiments, Y comprises a total number of Cysteine (C) of less than 4, or Y comprises a total number of Cysteine (C) of less than 3. In some embodiments, Y comprises a total number of Cysteine (C) of less than 4. In some embodiments, Y comprises a total number of Cysteine (C) of less than 3. In some embodiments, a total number of hydrophobic amino acids in Y is more than 8, the total number of hydrophobic amino acids in Y is more than 12, the total number of hydrophobic amino acids in Y is more than 15, and / or a total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, a total number of hydrophobic amino acids in Y is more than 8. In some embodiments, the total number of hydrophobic amino acids in Y is more than 12. In some embodiments, the total number of hydrophobic amino acids in Y is more than 15. In some embodiments, a total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85, or Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85.
[0078] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0079] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) , X-Y (II) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A, Y comprises a sequence having at most 90%identity with SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.
[0080] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) .
[0081] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) .
[0082] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) .
[0083] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) .
[0084] In some embodiments, at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H, and / or at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70%identity with SEQ ID NO: 1.
[0085] In some embodiments, Y comprises a sequence having at most 80%identity with SEQ ID NO: 2, or Y comprises a sequence having at most 70%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 80%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2. In some embodiments, a total number of hydrophobic amino acids in Y is more than 8, the total number of hydrophobic amino acids in Y is more than 12, the total number of hydrophobic amino acids in Y is more than 15, and / or a total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, a total number of hydrophobic amino acids in Y is more than 8. In some embodiments, the total number of hydrophobic amino acids in Y is more than 12. In some embodiments, the total number of hydrophobic amino acids in Y is more than 15. In some embodiments, a total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 16-18, or Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 16-18.
[0086] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0087] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) , X-Y (III) , wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E, Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2, a total number of H, R, K, D, Q, N and E in X is less than 33, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.
[0088] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) .
[0089] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) .
[0090] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) .
[0091] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) .
[0092] In some embodiments, at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H, and / or at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70%identity with SEQ ID NO: 1. In some embodiments, the total number of H, R, K, D, Q, N and E in X is less than 30, the total number of H, R, K, D, Q, N and E in X is less than 25, or the total number of H, R, K, D, Q, N and E in X is less than 20. In some embodiments, the total number of H, R, K, D, Q, N and E in X is less than 30. In some embodiments, the total number of H, R, K, D, Q, N and E in X is less than 25. In some embodiments, the total number of H, R, K, D, Q, N and E in X is less than 20. In some embodiments, a total number of hydrophilic amino acids in X is more than 10, a total number of hydrophilic amino acids in X is more than 15, a total number of hydrophilic amino acids in X is more than 20, a total number of hydrophilic amino acids in X is more than 25, a total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10. In some embodiments, a total number of hydrophilic amino acids in X is more than 10. In some embodiments, a total number of hydrophilic amino acids in X is more than 15. In some embodiments, a total number of hydrophilic amino acids in X is more than 20. In some embodiments, a total number of hydrophilic amino acids in X is more than 25. In some embodiments, a total number of hydrophobic amino acids in X is no more than 15. In some embodiments, the total number of hydrophobic amino acids in X is no more than 10.
[0093] In some embodiments, Y comprises a sequence having at least 90%identity with SEQ ID NO: 2, or Y comprises a sequence of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 90%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence of SEQ ID NO: 2. In some embodiments, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A.
[0094] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0095] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) , X-Y (IV) , wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E, Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2, X comprises a sequence having at most 90%identity with SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.
[0096] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) .
[0097] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) .
[0098] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) .
[0099] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) .
[0100] In some embodiments, at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H, and / or at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70%identity with SEQ ID NO: 1. In some embodiments, a total number of hydrophilic amino acids in X is more than 10, a total number of hydrophilic amino acids in X is more than 15, a total number of hydrophilic amino acids in X is more than 20, a total number of hydrophilic amino acids in X is more than 25, a total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10. In some embodiments, a total number of hydrophilic amino acids in X is more than 10. In some embodiments, a total number of hydrophilic amino acids in X is more than 15. In some embodiments, a total number of hydrophilic amino acids in X is more than 20. In some embodiments, a total number of hydrophilic amino acids in X is more than 25. In some embodiments, a total number of hydrophobic amino acids in X is no more than 15. In some embodiments, the total number of hydrophobic amino acids in X is no more than 10.
[0101] In some embodiments, Y comprises a sequence having at least 90%identity with SEQ ID NO: 2, or Y comprises a sequence of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 90%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence of SEQ ID NO: 2. In some embodiments, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A.
[0102] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0103] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) , X-Y (V) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.
[0104] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) .
[0105] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) .
[0106] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) .
[0107] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) .
[0108] In some embodiments, at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H, and / or at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70%identity with SEQ ID NO: 1.
[0109] In some embodiments, Y comprises 10 to 25 amino acids, Y comprises 10 to 20 amino acids, or Y comprises 10 to 15 amino acids. In some embodiments, Y comprises 10 to 25 amino acids. In some embodiments, Y comprises 10 to 20 amino acids. In some embodiments, Y comprises 10 to 15 amino acids. In some embodiments, Y comprises a sequence having at most 80%identity with SEQ ID NO: 2, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2, or Y comprises a sequence having at most 50%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 80%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 50%identity with SEQ ID NO: 2.
[0110] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0111] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.
[0112] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.
[0113] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.
[0114] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.
[0115] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.
[0116] In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74, the polypeptide is a polypeptide of any one of SEQ ID NOs: 28 and 62-74, or the polypeptide is a polypeptide of SEQ ID NO: 28. In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof. In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74. In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NOs: 28 and 62-74. In some embodiments, the polypeptide is a polypeptide of SEQ ID NO: 28.
[0117] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0118] In another aspect, provided is an artificial polypeptide of formula (I) , (II) , (III) , (IV) , (V) , (VI) , or (VII) , or a mutant of artificial polypeptide of (I) , (II) , (III) , (IV) or (V) , or a polypeptide having at least 70%identity with any one selected from SEQ ID NO. 28, SEQ ID NOs. 57 and 62-74 or a fragment or variant thereof, for use in preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, improving nerve conduction velocity in a subject in need thereof, increasing intraepidermal nerve fiber density in a subject in need thereof, or any combination thereof.
[0119] In another aspect, provided is use of an artificial polypeptide of formula (I) , (II) , (III) , (IV) , (V) , (VI) , or (VII) , or a mutant of artificial polypeptide of (I) , (II) , (III) , (IV) or (V) , or a polypeptide having at least 70%identity with any one selected from SEQ ID NO. 28, SEQ ID NOs. 57 and 62-74 or a fragment or variant thereof for the preparation of a medicament for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, improving nerve conduction velocity in a subject in need thereof, increasing intraepidermal nerve fiber density in a subject in need thereof, or any combination thereof.
[0120] In some embodiments, the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin. In some embodiments, the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel. In some embodiments, the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine. In some embodiments, the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin. In some embodiments, the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide. In some embodiments, the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib. In some embodiments, the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin. In some embodiments, the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) . In some embodiments, the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction. In some embodiments, the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy. In some embodiments, the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy. In some embodiments, the subject does not manifest peripheral neuropathic pain. In some embodiments, the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.
[0121] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the description are to be regarded as illustrative in nature, and not as restrictive.BRIEF DESCRIPTION OF THE DRAWINGS
[0122] Various features of this disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
[0123] Fig. 1 shows the motor conduction velocities of median nerves as measured according to Example 1.
[0124] Fig. 2 shows the change rates of the motor conduction of median nerves as measured according to Example 1.
[0125] Fig. 3 shows the sensory conduction velocities of median nerves as measured according to Example 1.
[0126] Fig. 4 shows the change rates of the sensory conduction of median nerves as measured according to Example 1.
[0127] Fig. 5 shows the motor conduction velocities of tibial nerves as measured according to Example 1.
[0128] Fig. 6 shows the results of conduction velocity tests for tail nerves 2 hours post administration on Day 21 as measured according to Example 2.
[0129] Fig. 7 shows the immunofluorescence staining images of epidermises of the right footpads of mice from various groups (20X) as measured according to Example 2.
[0130] Fig. 8 shows the IEFND values of mice from various groups 2 hours post administration on Day 22 as measured according to Example 2. INCORPORATION BY REFERENCE
[0131] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.DETAILED DESCRIPTIONDEFINITION
[0132] As used herein, the following terms have the meanings ascribed to them unless specified otherwise.
[0133] As used in the specification and claims, the singular forms “a, ” “an, ” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “acell” includes a plurality of cells, including mixtures thereof.
[0134] As used herein, the terms “comprise” , “include” , “contain” and variations thereof are intended to mean open-ended transitional phrases that do not exclude the possibilities of additional substances or methods. When such terms are used to describe a certain pharmaceutical composition, formulation, kit, use or method of the present disclosure, it also encompasses the situation that the pharmaceutical composition, formulation, kit, use or method consists of the recited substances or methods. For instance, the expression “the solvents comprise water” also includes the situation wherein the solvents are consisting of water, i.e., the solvents contain water exclusively. In the context of this disclosure, the term “consisting of” is intended to mean a close-ended transitional phrase, which excludes the possibilities of additional substances or methods.
[0135] As used herein, ranges as recited in this disclosure are intended to explicitly disclose each of the endpoints of the range and each integer included in the range, unless otherwise indicated. For example, “X is a moiety comprising 40 to 65 amino acids” means that the number of amino acids in the moiety of X can be 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64 or 65. For another example, “Y is a moiety comprising 10 to 50 amino acids” means that that the number of amino acids in moiety of Y can be 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50. Additionally, any sub-ranges consisting of these integers are intended to be included within the scope of this disclosure. Accordingly, “X is a moiety comprising 40 to 65 amino acids” is regarded as explicitly disclosing the sub-ranges such as “X is a moiety comprising 41 to 64 amino acids” , “X is a moiety comprising 42 to 63 amino acids” , “X is a moiety comprising 43 to 62 amino acids” , etc.
[0136] The term “about” or “approximately” herein means within an acceptable error range of the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” can mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, “about” can mean a range of up to 20%, up to 10%, up to 5%, or up to 1%of a given value. Where particular values are described in the application and claims, unless otherwise stated, the term “about” or “approximately” meaning within an acceptable error range for the particular value should be assumed.
[0137] The term "optional (ly) " means that the subsequently described event of circumstances may or may not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not.
[0138] The terms “polypeptide, ” “peptide, ” and “protein” are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified, for example, by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component.
[0139] The term “fragment” as used herein, when applied to a protein, refers to a truncated form of a native biologically active protein that may or may not retain at least a portion of the therapeutic and / or biological activity.
[0140] The term “variant” as used herein, when applied to a protein, refers to a protein with sequence homology to the native biologically active protein that retains at least a portion of the therapeutic and / or biological activity of the biologically active protein. For example, a variant protein may share at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%or 99%amino acid sequence identity as compared to the reference biologically active protein.
[0141] As used herein the term “amino acid (AA) ” refers to either natural and / or unnatural or synthetic amino acids, including but not limited to glycine and both the D or L optical isomers, and amino acid analogs and peptidomimetics. Standard single or three letter codes are used to designate amino acids.
[0142] The term “natural L-amino acid” means the L optical isomer forms of glycine (G) , proline (P) , alanine (A) , valine (V) , leucine (L) , isoleucine (I) , methionine (M) , cysteine (C) , phenylalanine (F) , tyrosine (Y) , tryptophan (W) , histidine (H) , lysine (K) , arginine (R) , glutamine (Q) , asparagine (N) , glutamic acid (E) , aspartic acid (D) , serine (S) , and threonine (T) .
[0143] The terms “hydrophilic” and “hydrophobic” refer to the degree of affinity that a substance has with water. A hydrophilic substance has a strong affinity for water, tending to dissolve in, mix with, or be wetted by water, while a hydrophobic substance substantially lacks affinity for water, tending to repel and not absorb water and tending not to dissolve in or mix with or be wetted by water. Amino acids can be characterized based on their hydrophobicity. Examples of “hydrophilic amino acids” are arginine, lysine, threonine, alanine, asparagine, and glutamine. Of particular interest are the hydrophilic amino acids aspartate, glutamate, serine, and glycine. In some embodiments, “hydrophilic amino acids” refers to arginine, lysine, threonine, alanine, asparagine, glutamine, aspartate, glutamate, serine, and glycine. Examples of “hydrophobic amino acids” are tryptophan, tyrosine, phenylalanine, methionine, leucine, isoleucine, and valine. In some embodiments, “hydrophobic amino acids” refers to tryptophan, tyrosine, phenylalanine, methionine, leucine, isoleucine, and valine.
[0144] A “host cell” includes an individual cell or cell culture which can be or has been a recipient for the subject vectors. Host cells include progeny of a single host cell. The progeny may not necessarily be completely identical (in morphology or in genomic of total DNA complement) to the original parent cell.
[0145] “Conjugated” , “linked, ” “fused, ” and “fusion” are used interchangeably herein. These terms refer to the joining together of two more chemical elements or components, by whatever means including chemical conjugation or recombinant means.
[0146] The terms “polynucleotides” , “nucleic acids” , “nucleotides” and “oligonucleotides” are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three-dimensional structure, and may perform any function, known or unknown. The following are non-limiting examples of polynucleotides: coding or non-coding regions of a gene or gene fragment, loci (locus) defined from linkage analysis, exons, introns, messenger RNA (mRNA) , transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure may be imparted before or after assembly of the polymer. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component.
[0147] The term “complement of a polynucleotide” denotes a polynucleotide molecule having a complementary base sequence and reverse orientation as compared to a reference sequence, such that it could hybridize with a reference sequence with complete fidelity.
[0148] The term “recombinant” as applied to a polynucleotide means that the polynucleotide is the product of various combinations of in vitro cloning, restriction and / or ligation steps, and other procedures that result in a construct that can potentially be expressed in a host cell.
[0149] The term “homology” or “homologous” refers to sequence similarity or interchangeability between two or more polynucleotide sequences or two or more polypeptide sequences. When using a program such as BestFit to determine sequence identity, similarity or homology between two different amino acid sequences, the default settings may be used, or an appropriate scoring matrix, such as blosum45 or blosum80, may be selected to optimize identity, similarity or homology scores. Preferably, polynucleotides that are homologous are those which hybridize under stringent conditions as defined herein and have at least 70%, preferably at least 80%, more preferably at least 90%, more preferably 95%, more preferably 97%, more preferably 98%, and even more preferably 99%sequence identity to those sequences.
[0150] The terms “percent identity” and “%identity” , as applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm. Such an algorithm may insert, in a standardized and reproducible way, gaps in the sequences being compared in order to optimize alignment between two sequences, and therefore achieve a more meaningful comparison of the two sequences. Percent identity may be measured over the length of an entire defined polynucleotide sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polynucleotide sequence, for instance, a fragment of at least 45, at least 60, at least 90, at least 120, at least 150, at least 210 or at least 450 contiguous residues. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures or Sequence Listing, may be used to describe a length over which percentage identity may be measured.
[0151] “Percent (%) amino acid sequence identity” , with respect to the polypeptide sequences identified herein, is defined as the percentage of amino acid residues in a query sequence that are identical with the amino acid residues of a second, reference polypeptide sequence or a portion thereof, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. Percent identity may be measured over the length of an entire defined polypeptide sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polypeptide sequence, for instance, a fragment of at least 15, at least 20, at least 30, at least 40, at least 50, at least 70 or at least 150 contiguous residues. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures or Sequence Listing, may be used to describe a length over which percentage identity may be measured.
[0152] A “vector” is a nucleic acid molecule, preferably self-replicating in an appropriate host, which transfers an inserted nucleic acid molecule into and / or between host cells. The term includes vectors that function primarily for insertion of DNA or RNA into a cell, replication of vectors that function primarily for the replication of DNA or RNA, and expression vectors that function for transcription and / or translation of the DNA or RNA. Also included are vectors that provide more than one of the above functions. An “expression vector” is a polynucleotide which, when introduced into an appropriate host cell, can be transcribed and translated into a polypeptide (s) . An “expression system” usually connotes a suitable host cell comprised of an expression vector that can function to yield a desired expression product.
[0153] The term “physiological conditions” refers to a set of conditions in a living host as well as in vitro conditions, including temperature, salt concentration, pH, that mimic those conditions of a living subject. A host of physiologically relevant conditions for use in in vitro assays have been established. Generally, a physiological buffer contains a physiological concentration of salt and is adjusted to a neutral pH ranging from about 6.5 to about 7.8, and preferably from about 7.0 to about 7.5. A variety of physiological buffers is listed in Sambrook et al. (1989) . Physiologically relevant temperature ranges from about 25 ℃ to about 38 ℃, and preferably from about 35 ℃ to about 37 ℃.
[0154] The term “antagonist” as used herein, includes any molecule that partially or fully blocks, inhibits, or neutralizes a biological activity of a native polypeptide disclosed herein. Methods for identifying antagonists of a polypeptide may comprise contacting a native polypeptide with a candidate antagonist molecule and measuring a detectable change in one or more biological activities normally associated with the native polypeptide. In the context of the present disclosure, antagonists may include proteins, nucleic acids, carbohydrates, antibodies or any other molecules that decrease the effect of a biologically active protein.
[0155] The term “agonist” is used in the broadest sense and includes any molecule that mimics a biological activity of a native polypeptide disclosed herein. Suitable agonist molecules specifically include agonist antibodies or antibody fragments, fragments or amino acid sequence variants of native polypeptides, peptides, small organic molecules, etc. Methods for identifying agonists of a native polypeptide may comprise contacting a native polypeptide with a candidate agonist molecule and measuring a detectable change in one or more biological activities normally associated with the native polypeptide.
[0156] The term “activity” for the purposes herein refers to an action or effect of a component of a fusion protein consistent with that of the corresponding native biologically active protein, wherein “biological activity” refers to an in vitro or in vivo biological function or effect, including but not limited to receptor binding, antagonist activity, agonist activity, or a cellular or physiologic response.
[0157] As used herein, “treatment” or “treating, ” “palliating, ” and “ameliorating” are used interchangeably. These terms refer to an approach for obtaining beneficial or desired results including but not limited to a therapeutic benefit and / or a prophylactic benefit. By “therapeutic benefit” is meant eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disease condition such that an improvement is observed in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder. For prophylactic benefit, the compositions may be administered to a subject at risk of developing a particular disease condition, or to a subject reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease may not have been made.
[0158] The term “therapeutic effect” refers to a physiologic effect, including but not limited to the cure, mitigation, amelioration, or prevention of disease condition in humans or other animals, or to otherwise enhance physical or mental wellbeing of humans or animals, caused by a polypeptide of the present disclosure. Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.
[0159] The term “effective amount” refers to an amount of a biologically active protein, either alone or as a part of a fusion protein composition, that is capable of having any detectable, beneficial effect on any symptom, aspect, measured parameter or characteristics of a disease state or condition when administered in one or repeated doses to a subject. Such effect need not be absolute to be beneficial. The disease condition can refer to a disorder or a disease.
[0160] The term “pharmaceutically acceptable” refers to those compounds, materials, compositions, formulations or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and other animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.
[0161] The terms “formulation” and “dosage form” are used interchangeably and refer to a pharmaceutical composition that is formulated in accordance with clinical requirements, in a form that can be directly administered to a subject in need thereof for preventive or therapeutic use.
[0162] The term “pharmaceutically acceptable excipient” refers to a pharmaceutically acceptable material, carrier, or vehicle which are used for the preparation of the formulations or dosage forms in accordance with the present disclosure. Each excipient must be “acceptable” in the sense of being compatible with the other ingredients of the formulations or dosage forms and not injurious to the patient.
[0163] The term “subject” “individual” or “patient” as used herein refers to any animals that can be used in the present disclosure, including but not limited to human, primate, rodent, canine, feline, equine, ovine, porcine, and the like.
[0164] The terms “administer” , “administered” , “administers” , “administering” and “dosing” are used interchangeably and are defined as providing a compound, a composition, a formulation and / or a dosage form in accordance with the present disclosure to a subject in need thereof via a route known in the art, including but not limited to oral, buccal, topical, transmucosal, transdermal, rectal, and parenteral routes of administration. In some embodiments, an oral route of administration is used. In some embodiments, a parenteral route of administration, including intravenous, intraarterial, intramuscular, subcutaneous, intraosseous, and intraperitoneal is used. In some embodiments, a topical route of administration is used.
[0165] The term “in vivo” as used herein refers to an event that takes place in a subject’s body.
[0166] The term “in vitro” as used herein refers to an event that takes places outside of a subject’s body. In some embodiments, an in vitro assay encompasses any assay run outside of a subject assay. In vitro assays encompass cell-based assays in which cells alive or dead are employed. In vitro assays also encompass a cell-free assay in which no intact cells are employed.
[0167] The term “peripheral neuropathy” as used herein refers to a common type of conditions that involve damage to the peripheral nervous system, which is a vast communications network which sends signals between the central nervous system and all other parts of the body. Damage to the peripheral nervous system may impair sensation, movement, gland function, and / or organ function, depending on the nerves being affected. Different symptoms may result from peripheral neuropathy affecting motor, sensory, or autonomic nerves.
[0168] The term “nerve injury” as used herein refers to an injury to a nerve. Injury to a nerve can stop signals to and from the brain, and can in turn cause muscles to stop working properly and lead to loss of feeling. Peripheral neuropathy is often accompanied by nerve injury, which can affect nerve cells, nerve fibers, nerve conduction, etc.
[0169] The term “neuroprotection” as used herein refers to the relative preservation of neuronal structure and / or function. The aim of neuroprotection is to prevent or slow progression of disease and secondary injuries by halting or at least slowing the loss of neurons.
[0170] The term “neuroprotective agent” as used herein refers to an agent that has neuroprotective function. Neuroprotective agents are needed in subjects afflicted by clinical conditions in which nerve injury is implicated.
[0171] The term “neuroregeneration” as used herein refers to the regrowth or repair of nervous tissues, cells or cell products, the mechanisms of which may include the generation of new neurons, glia, axons, myelin, or synapses.
[0172] The term “nervous tissue” as used herein refers to the main tissue component of the nervous system. It is composed of neurons, also termed as nerve cells, which receive and transmit impulses, and neuroglia, also termed as glial cells or glia, which assist the propagation of the nerve impulse as well as provide nutrients to the neurons.
[0173] The term “cell damage” as used herein refers to a variety of changes of stress that a cell suffers due to external as well as internal environmental changes.
[0174] The term “inflammatory response” as used herein refers to part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants.
[0175] The term “nerve conduction velocity” as used herein refers to the rate at which nerve signals travel along a nerve or nerve fiber. Usually, it is measured in meters per second (m / s) . Impaired nerve conduction velocity is considered a very unique symptom of neuropathy, and medications used for treating neuralgia are generally not used to treat impaired nerve conduction velocity.
[0176] The term “intraepidermal nerve fiber density (IEFND) ” as used herein refers to the density of nerves in the outer layer of the skin. IEFND is a measure used to assess the extent of neuropathy. To assess IEFND, the number of nerve fibers in skin biopsy samples is determined. An increase in the number / density of intraepidermal nerve fibers indicates improvement in neuropathy.
[0177] The term “diabetic peripheral neuropathy (DPN) ” as used herein refers to a long-term major complication of diabetes mellitus, in which exposure to high blood glucose levels over an extended period of time causes damage to the peripheral nerves going to the arms, hands, legs, and feet.
[0178] The term “chemotherapy-induced peripheral neuropathy (CIPN) ” as used herein refers to is a nerve-damaging side effect of antitumor agents in chemotherapy. Antitumor agents can cause injuries to healthy structures, including the peripheral nervous system. CIPN involves various symptoms such as tingling, pain, and numbness in the hands and feet, impairing activities of daily living of the patients. METHODS OF TREATMENT AND THERAPEUTIC USES
[0179] In one aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) : X-Y (I) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, and Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A; wherein Y comprises a total number of Cysteine (C) of less than 5.
[0180] In one aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) .
[0181] In one aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) .
[0182] In one aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) .
[0183] In one aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) .
[0184] In some embodiments, X of formula (I) can be a hydrophilic moiety, at least 50%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) can be a hydrophilic moiety, at least 55%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) can be a hydrophilic moiety, at least 60%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) can be a hydrophilic moiety, at least 65%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) can be a hydrophilic moiety, at least 70%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) can be a hydrophilic moiety, at least 75%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) can be a hydrophilic moiety, at least 80%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) can be a hydrophilic moiety, at least 85%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) can be a hydrophilic moiety, at least 90%of which are selected from R, K, N, D, Q, E, and H.
[0185] In some embodiments, X of formula (I) can be a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 85%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 95%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising the sequence of SEQ ID NO: 1. In some embodiments, X is a moiety that is the sequence of SEQ ID NO: 1.
[0186] In some embodiments, Y of formula (I) can be a hydrophobic moiety, at least 50%of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) can be a hydrophobic moiety, at least 55%of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) can be a hydrophobic moiety, at least 60%of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) can be a hydrophobic moiety, at least 65%of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) can be a hydrophobic moiety, at least 70%of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) can be a hydrophobic moiety, at least 75%of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) can be a hydrophobic moiety, at least 80%of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) can be a hydrophobic moiety, at least 85%of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) can be a hydrophobic moiety, at least 90%of which are selected from I, V, L, F, C, M, and A.
[0187] In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 5. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 5. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 6. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 6. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 7. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 7. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 8. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 8. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 9. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 9. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 10. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 10. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 11. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 11. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 12. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 12. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 13. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 13. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 14. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 14. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is 15. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of hydrophobic amino acids of Y is more than 15.
[0188] In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 5. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 5. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 6. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 6. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 7. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 7. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 8. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 8. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 9. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 9. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 10. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 10. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 11. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 11. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 12. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 12. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 13. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 13. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 14. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 14. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is 15. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of I, V, L, F, C, M, and A of Y is more than 15.
[0189] In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 5. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is less than 5. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 4. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is less than 4. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 3. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is less than 3. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 2. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is less than 2. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 1. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is less than 1. In some embodiments, Y of formula (I) can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 0.
[0190] In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is 5. In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is no more than 5. In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is 4. In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is no more than 4. In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is 3. In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is no more than 3. In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is 2. In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is no more than 2. In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is 1. In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is no more than 1.
[0191] In some embodiments, a total number of R, K, N, D, Q, E, and H in Y of formula (I) is 5. In some embodiments, a total number of R, K, N, D, Q, E, and H in Y of formula (I) is no more than 5. In some embodiments, a total number of hydrophilic amino acids in Y of formula (I) is 4. In some embodiments, a total number of R, K, N, D, Q, E, and H in Y of formula (I) is no more than 4. In some embodiments, a total number of R, K, N, D, Q, E, and H in Y of formula (I) is 3. In some embodiments, a total number of R, K, N, D, Q, E, and H in Y of formula (I) is no more than 3. In some embodiments, a total number of R, K, N, D, Q, E, and H in Y of formula (I) is 2. In some embodiments, a total number of R, K, N, D, Q, E, and H in Y of formula (I) is no more than 2. In some embodiments, a total number of R, K, N, D, Q, E, and H in Y of formula (I) is 1. In some embodiments, a total number of R, K, N, D, Q, E, and H in Y of formula (I) is no more than 1.
[0192] In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence of any one selected from SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) is a sequence of any one selected from SEQ ID NOs: 81-83.
[0193] In some embodiments of the artificial polypeptide, Y of formula (I) comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments of the artificial polypeptide, Y of formula (I) comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments of the artificial polypeptide, Y of formula (I) comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments of the artificial polypeptide, Y of formula (I) comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments of the artificial polypeptide, Y of formula (I) comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments of the artificial polypeptide, Y of formula (I) comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments of the artificial polypeptide, Y of formula (I) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments of the artificial polypeptide, Y of formula (I) comprises a sequence of any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments of the artificial polypeptide, Y of formula (I) is a sequence of any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85.
[0194] In some embodiments of the artificial polypeptide of formula (I) , the polypeptide comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 29-41, 54-57, 75 and 91-95.In some embodiments of the artificial polypeptide of formula (I) , the polypeptide comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I) , the polypeptide comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I) , the polypeptide comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I) , the polypeptide comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I) , the polypeptide comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I) , the polypeptide comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I) , the polypeptide comprises a sequence of any one of SEQ ID NOs: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I) , the polypeptide is a sequence of any one of SEQ ID NOs: 29-41, 54-57, 75 and 91-95.
[0195] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) : X-Y (II) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, and Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A; wherein Y comprises a sequence having at most 90%identity with SEQ ID NO: 2.
[0196] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) .
[0197] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) .
[0198] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) .
[0199] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) .
[0200] In some embodiments, X of formula (II) can be a hydrophilic moiety, at least 50%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) can be a hydrophilic moiety, at least 55%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) can be a hydrophilic moiety, at least 60%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) can be a hydrophilic moiety, at least 65%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) can be a hydrophilic moiety, at least 70%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of (II) can be a hydrophilic moiety, at least 75%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) can be a hydrophilic moiety, at least 80%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) can be a hydrophilic moiety, at least 85%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) can be a hydrophilic moiety, at least 90%of which are selected from R, K, N, D, Q, E, and H.
[0201] In some embodiments, X of formula (II) can be a hydrophilic moiety comprising one or more Arginine (R) . For example, X of formula (II) can be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten Arginine (R) . In some embodiments, X of formula (II) can be a hydrophilic moiety comprising one or more Lysine (K) . For example, X of formula (II) can be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten Lysine (K) . In some embodiments, X of formula (II) can be a hydrophilic moiety comprising one or more Asparagine (N) . For example, X of formula (II) can be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten Asparagine (N) . In some embodiments, X of formula (II) can be a hydrophilic moiety comprising one or more Aspartic Acid (D) . For example, X of formula (II) can be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten Aspartic Acid (D) . In some embodiments, X of formula (II) can be a hydrophilic moiety comprising one or more Glutamine (Q) . For example, X of formula (II) can be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten Glutamine (Q) . In some embodiments, X of formula (II) can be a hydrophilic moiety comprising one or more Glutamic Acid (E) . For example, X of formula (II) can be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten Glutamic Acid (E) . In some embodiments, X of formula (II) can be a hydrophilic moiety comprising one or more Histidine (H) . For example, X of formula (II) can be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten Histidine (H) .
[0202] In some embodiments, X of formula (II) can be a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 85%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 95%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising the sequence of SEQ ID NO: 1. In some embodiments, X is a moiety that is the sequence of SEQ ID NO: 1.
[0203] In some embodiments of the artificial polypeptide of formula (II) , Y comprises a sequence having at most 50%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 55%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 60%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 65%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 75%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 80%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 85%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 90%identity with SEQ ID NO: 2.
[0204] In some embodiments of the artificial polypeptide of formula (II) , Y comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence of any one selected from SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y is a sequence of any one selected from SEQ ID NOs: 16-18.
[0205] In some embodiments of the artificial polypeptide of formula (II) , the artificial polypeptide comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence of any one selected from SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide is a sequence of any one selected from SEQ ID NOs: 42-44.
[0206] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) : X-Y (III) , wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; and Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2, wherein a total number of H, R, K, D, Q, N and E in X is less than 33.
[0207] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) .
[0208] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) .
[0209] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) .
[0210] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) .
[0211] In some embodiments, X of formula (III) is hydrophilic moiety, at least 50%of which are selected from H, R, K, D, Q, N and E. In some embodiments, X of formula (III) can be a hydrophilic moiety, at least 55%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (III) can be a hydrophilic moiety, at least 60%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (III) can be a hydrophilic moiety, at least 65%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (III) can be a hydrophilic moiety, at least 70%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (III) can be a hydrophilic moiety, at least 75%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (III) can be a hydrophilic moiety, at least 80%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (III) can be a hydrophilic moiety, at least 85%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (III) can be a hydrophilic moiety, at least 90%of which are selected from R, K, N, D, Q, E, and H.
[0212] In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 33. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 32. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 31. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 30. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 29. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 28. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 27. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 26. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 25. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 24. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 23. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 22. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 21. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 20.
[0213] In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 10. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 11. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 12. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 13. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 14. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 15. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 16. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 17. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 18. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 19. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 20. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 21. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 22. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 23. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 24. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 25.
[0214] In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 15. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 14. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 13. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 12. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 11. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 10. In some embodiments, X of formula (III) is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 5.
[0215] In some embodiments, X of formula (III) comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 23-27. In some embodiments, X of formula (III) comprises a sequence of any one selected from SEQ ID NOs: 23-27. In some embodiments, X of formula (III) is a sequence of any one selected from SEQ ID NOs: 23-27.
[0216] In some embodiments, Y of formula (III) is a moiety comprising a sequence having at least 70%identity with SEQ ID NO: 2. In some embodiments, Y of formula (III) is a moiety comprising a sequence having at least 75%identity with SEQ ID NO: 2. In some embodiments, Y of formula (III) is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2. In some embodiments, Y of formula (III) is a moiety comprising a sequence having at least 85%identity with SEQ ID NO: 2. In some embodiments, Y of formula (III) is a moiety comprising a sequence having at least 90%identity with SEQ ID NO: 2. In some embodiments, Y of formula (III) is a moiety comprising a sequence having at least 95%identity with SEQ ID NO: 2. In some embodiments, Y of formula (III) is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with SEQ ID NO: 2. In some embodiments, Y of formula (III) is a moiety comprising a sequence of SEQ ID NO: 2. In some embodiments, Y of formula (III) is a moiety that is a sequence of SEQ ID NO: 2.
[0217] In some embodiments, Y of formula (III) is hydrophobic moiety, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is hydrophobic moiety, at least 55%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is hydrophobic moiety, at least 60%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is hydrophobic moiety, at least 65%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is hydrophobic moiety, at least 70%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is hydrophobic moiety, at least 75%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is hydrophobic moiety, at least 80%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is hydrophobic moiety, at least 85%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is hydrophobic moiety, at least 90%amino acids of Y are selected from I, V, L, F, C, M, and A.
[0218] In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence of any one selected from SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of formula (III) is a sequence of any one selected from SEQ ID NOs: 49-53.
[0219] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) : X-Y (IV) , wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; and Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2, wherein X comprises a sequence having at most 90%identity with SEQ ID NO: 1.
[0220] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) .
[0221] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) .
[0222] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) .
[0223] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) .
[0224] In some embodiments, X of formula (IV) is a hydrophilic moiety, at least 50%of which are selected from H, R, K, D, Q, N and E. In some embodiments, X of formula (IV) can be a hydrophilic moiety, at least 55%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) can be a hydrophilic moiety, at least 60%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) can be a hydrophilic moiety, at least 65%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) can be a hydrophilic moiety, at least 70%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) can be a hydrophilic moiety, at least 75%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) can be a hydrophilic moiety, at least 80%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) can be a hydrophilic moiety, at least 85%of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) can be a hydrophilic moiety, at least 90%of which are selected from R, K, N, D, Q, E, and H.
[0225] In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 10. In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 15. In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 20. In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 25. In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 30. In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 35.
[0226] In some embodiments, X of formula (IV) comprises a sequence having at most 50%identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 55%identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 60%identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 65%identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 70%identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 75%identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 80%identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 85%identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 90%identity with SEQ ID NO: 1.
[0227] In some embodiments, Y of formula (IV) is a moiety comprising a sequence having at least 70%identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a moiety comprising a sequence having at least 75%identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a moiety comprising a sequence having at least 85%identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a moiety comprising a sequence having at least 90%identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a moiety comprising a sequence having at least 95%identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a moiety comprising a sequence of SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a moiety that is a sequence of SEQ ID NO: 2.
[0228] In some embodiments, Y of formula (IV) is hydrophobic moiety, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (IV) is hydrophobic moiety, at least 55%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (IV) is hydrophobic moiety, at least 60%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (IV) is hydrophobic moiety, at least 65%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (IV) is hydrophobic moiety, at least 70%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (IV) is hydrophobic moiety, at least 75%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (IV) is hydrophobic moiety, at least 80%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (IV) is hydrophobic moiety, at least 85%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (IV) is hydrophobic moiety, at least 90%amino acids of Y are selected from I, V, L, F, C, M, and A.
[0229] In some embodiments, X of formula (IV) comprises a sequence having at least 70%identity with any one selected from SEQ IDs NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 75%identity with any one selected from SEQ IDs NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 80%identity with any one selected from SEQ IDs NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 85%identity with any one selected from SEQ IDs NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 90%identity with any one selected from SEQ IDs NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 95%identity with any one selected from SEQ IDs NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ IDs NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence of any one selected from SEQ IDs NO. 19-22 and 76-79. In some embodiments, X of formula (IV) is a sequence of any one selected from SEQ IDs NO. 19-22 and 76-79.
[0230] In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence of any one selected from SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) is a sequence of any one selected from SEQ ID NOs: 45-48 and 86-89.
[0231] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) : X-Y (V) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, and Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2.
[0232] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) .
[0233] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) .
[0234] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) .
[0235] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) .
[0236] In some embodiments, Y of formula (V) comprises 10 to 25 amino acids. In some embodiments, Y comprises 10 to 20 amino acids. In some embodiments, Y comprises 10 to 15 amino acids. In some embodiments, Y comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 amino acids.
[0237] In some embodiments, X of formula (V) can be a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 85%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 95%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with SEQ ID NO: 1. In some embodiments, X is a moiety comprising the sequence of SEQ ID NO: 1. In some embodiments, X is a moiety that is the sequence of SEQ ID NO: 1.
[0238] In some embodiments of the artificial polypeptide of formula (V) , at least 50%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 55%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 60%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 65%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 70%amino acids of X are selected from R, K, N, D, Q, E, and H.In some embodiments, at least 75%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 80%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 85%amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 90%amino acids of X are selected from R, K, N, D, Q, E, and H.
[0239] In some embodiments of the artificial polypeptide of formula (V) , X comprises a sequence having at least 70%identity with SEQ ID NO: 96. In some embodiments of the artificial polypeptide of formula (V) , X comprises a sequence having at least 75%identity with SEQ ID NO: 96. In some embodiments of the artificial polypeptide of formula (V) , X comprises a sequence having at least 80%identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 85%identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 90%identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 95%identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence of SEQ ID NO: 96. In some embodiments, X is a sequence of SEQ ID NO: 96.
[0240] In some embodiments of the artificial polypeptide of formula (V) , Y comprises a sequence having at most 50%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 55%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 60%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 65%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 75%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 80%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 85%identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 90%identity with SEQ ID NO: 2.
[0241] In some embodiments of the artificial polypeptide of formula (V) , Y comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments of the artificial polypeptide of formula (V) , Y comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments of the artificial polypeptide of formula (V) , Y comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence that is any one selected from SEQ ID NOs: 97-103. In some embodiments, Y is a sequence that is any one selected from SEQ ID NOs: 97-103.
[0242] In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence of any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) is a sequence of any one selected from SEQ ID NOs: 53-56 and 104-110.
[0243] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) : X-Y (VI) , wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in SEQ ID NO: 1 mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in SEQ ID NO: 1 mutated to T; and Y is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, or 5 C in SEQ ID NO: 2 mutated to A.
[0244] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) .
[0245] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) .
[0246] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) .
[0247] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) .
[0248] In some embodiments, X of formula (VI) comprises a sequence having at least 70%identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at least 75%identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at least 80%identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at least 85%identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at least 95%identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at most 95%identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at most 90%identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at most 85%identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at most 80%identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at most 75%identity with SEQ ID NO: 1.
[0249] In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 70%identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 75%identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 85%identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 90%identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 95%identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) comprises a sequence having at most 95%identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) comprises a sequence having at most 90%identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) comprises a sequence having at most 85%identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) comprises a sequence having at most 80%identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) comprises a sequence having at most 75%identity with SEQ ID NO: 2.
[0250] In some embodiments, Y of formula (VI) is hydrophobic moiety, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is hydrophobic moiety, at least 55%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is hydrophobic moiety, at least 60%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is hydrophobic moiety, at least 65%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is hydrophobic moiety, at least 70%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is hydrophobic moiety, at least 75%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is hydrophobic moiety, at least 80%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is hydrophobic moiety, at least 85%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is hydrophobic moiety, at least 90%amino acids of Y are selected from I, V, L, F, C, M, and A.
[0251] In some embodiments, X of formula (VI) is a moiety comprising 40 to 65 amino acids, and a total number of R, K, T, A, N, Q, D, E, S, and G in X is more than 30. In some embodiments, X of formula (VI) is a moiety comprising 40 to 65 amino acids, and a total number of R, K, T, A, N, Q, D, E, S, and G in X is 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40. In some embodiments, X of formula (VI) is a moiety comprising 40 to 65 amino acids, and a total number of W, Y, F, M, L, I, and V in X is no more than 20. In some embodiments, X of formula (VI) is a moiety comprising 40 to 65 amino acids, and a total number of W, Y, F, M, L, I, and V in X is 19, 18, 17, 16, 15 or 14.
[0252] In some embodiments, Y of formula (VI) is a moiety comprising 10 to 50 amino acids, and a total number of R, K, T, A, N, Q, D, E, S, and G in Y is more than 10. In some embodiments, Y of formula (VI) is a moiety comprising 10 to 50 amino acids, and a total number of R, K, T, A, N, Q, D, E, S, and G in Y is 11, 12, 13, 14 or 15. In some embodiments, Y of formula (VI) is a moiety comprising 10 to 50 amino acids, and a total number of W, Y, F, M, L, I, and V in X is no more than 20. In some embodiments, Y of formula (VI) is a moiety comprising 10 to 50 amino acids, and a total number of W, Y, F, M, L, I, and V in Y is 19, 18, 17, 16, 15 or 14.
[0253] In some embodiments, X of formula (VI) comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 80-83. In some embodiments, X of formula (VI) comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 80-83. In some embodiments, X of formula (VI) comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 80-83. In some embodiments, X of formula (VI) comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 80-83. In some embodiments, X of formula (VI) comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 80-83. In some embodiments, X of formula (VI) comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 80-83. In some embodiments, X of formula (VI) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 80-83. In some embodiments, X of formula (VI) comprises a sequence of any one selected from SEQ ID NOs: 80-83. In some embodiments, X of formula (VI) is a sequence of any one selected from SEQ ID NOs: 80-83.
[0254] In some embodiments, Y of formula (VI) comprises a sequence having at least 70%identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 75%identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 80%identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 85%identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 90%identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 95%identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence of SEQ ID NO: 3. In some embodiments, Y of formula (VI) is a sequence of SEQ ID NO: 3.
[0255] In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence that is any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide of formula (VI) is a sequence that is any one selected from SEQ ID NOs: 90-93.
[0256] In one aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) : X-Y (VII) , wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1, and Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 continuous AAs of SEQ ID NO: 2.
[0257] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) .
[0258] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) .
[0259] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) .
[0260] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) .
[0261] In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1 amino acid insertion relative to SEQ ID NO: 1. In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has 1 amino acid insertion relative to SEQ ID NO: 1. In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 2 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has 2 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 3 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has 3 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 4 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has 4 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 5 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has 5 amino acid insertions relative to SEQ ID NO: 1.
[0262] In some embodiments, at least 20%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H.
[0263] In some embodiments, Y is a moiety comprising 10 to 30 amino acids. In some embodiments, Y is a moiety comprising 10 amino acids, 11 amino acids, 12 amino acids, 13 amino acids, 14 amino acids, 15 amino acids, 16 amino acids, 17 amino acids, 18 amino acids, 19 amino acids, 20 amino acids, 21 amino acids, 22 amino acids, 23 amino acids, 24 amino acids, 25 amino acids, 26 amino acids, 27 amino acids, 28 amino acids, 29 amino acids, or 30 amino acids. In some embodiments, Y is a moiety comprising 11 to 29 amino acids. In some embodiments, Y is a moiety comprising 12 to 28 amino acids. In some embodiments, Y is a moiety comprising 13 to 27 amino acids. In some embodiments, Y is a moiety comprising 14 to 26 amino acids. In some embodiments, Y is a moiety comprising 15 to 25 amino acids. In some embodiments, Y comprises 15 to 25 amino acids. In some embodiments, Y comprises 18 to 25 amino acids. In some embodiments, Y comprises 20 to 25 amino acids.
[0264] In some embodiments, Y comprises a sequence having at least 15 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 15 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 16 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 16 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 17 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 17 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 18 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 18 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 19 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 19 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 20 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 20 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 21 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 21 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 22 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 22 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 23 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 23 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 24 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 24 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 25 continuous AAs of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having 25 continuous AAs of SEQ ID NO: 2.
[0265] In some embodiments, Y is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations relative to SEQ ID NO: 2. In some embodiments, the at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations are located at the C-terminal of Y. In some embodiments, Y is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations relative to SEQ ID NO: 2. In some embodiments, the 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations are located at the C-terminal of Y.
[0266] In some embodiments, a total number of E or D in X is at least 8. In some embodiments, a total number of E or D in X is 8. In some embodiments, a total number of E or D in X is at least 9. In some embodiments, a total number of E or D in X is 9. In some embodiments, a total number of E or D in X is at least 10. In some embodiments, a total number of E or D in X is 10. In some embodiments, a total number of E or D in X is at least 11. In some embodiments, a total number of E or D in X is 11. In some embodiments, a total number of E or D in X is at least 12. In some embodiments, a total number of E or D in X is 12. In some embodiments, a total number of E or D in X is at most 15. In some embodiments, a total number of E or D in X is 15. In some embodiments, a total number of E or D in X is at most 14. In some embodiments, a total number of E or D in X is 14. In some embodiments, a total number of E or D in X is at most 13. In some embodiments, a total number of E or D in X is 13. In some embodiments, a total number of E or D in X is at most 12. In some embodiments, a total number of E or D in X is 12. In some embodiments, a total number of E or D in X is at most 11. In some embodiments, a total number of E or D in X is 11. In some embodiments, a total number of E or D in X is at most 10. In some embodiments, a total number of E or D in X is 10.
[0267] In some embodiments, X of formula (VII) is a moiety comprising 40 to 65 amino acids, and a total number of R, K, T, A, N, Q, D, E, S, and G in X is more than 30. In some embodiments, X of formula (VII) is a moiety comprising 40 to 65 amino acids, and a total number of R, K, T, A, N, Q, D, E, S, and G in X is 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40. In some embodiments, X of formula (VII) is a moiety comprising 40 to 65 amino acids, and a total number of W, Y, F, M, L, I, and V in X is no more than 20. In some embodiments, X of formula (VII) is a moiety comprising 40 to 65 amino acids, and a total number of W, Y, F, M, L, I, and V in X is 19, 18, 17, 16, 15 or 14.
[0268] In some embodiments, 40-65%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 40%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 45%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 55%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 60%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at most 65%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at most 60%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at most 55%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at most 50%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at most 45%amino acids of Y are selected from I, V, L, F, C, M, and A.
[0269] In some embodiments, a total number of R, K, T, A, N, Q, D, E, S, and G in Y is no more than 10. In some embodiments, a total number of R, K, T, A, N, Q, D, E, S, and G in Y is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some embodiments, a total number of W, Y, F, M, L, I, and V in Y is no more than 15. In some embodiments, a total number of W, Y, F, M, L, I, and V in Y is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15.
[0270] In some embodiments, X of formula (VII) comprises a sequence having at least 70%identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence having at least 75%identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence having at least 80%identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence having at least 85%identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence having at least 90%identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence having at least 95%identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence of SEQ ID NO: 96. In some embodiments, X of formula (VII) is a sequence of SEQ ID NO: 96.
[0271] In some embodiments, Y of formula (VII) comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence that is any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) is a sequence that is any one selected from SEQ ID NOs: 97-103.
[0272] In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence that is any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of formula (VII) is a sequence that is any one selected from SEQ ID NOs: 104-110.
[0273] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) , X-Y (I) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A, Y comprises a total number of Cysteine (C) of less than 5, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.
[0274] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) .
[0275] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) .
[0276] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) .
[0277] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) .
[0278] In some embodiments, at least 20%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H.
[0279] In some embodiments, X in the mutant comprises a sequence having at least 70%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 75%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 80%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 85%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 95%identity with SEQ ID NO: 1.
[0280] In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 5. In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is less than 5. In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 4. In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is less than 4. In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 3. In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is less than 3. In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 2. In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is less than 2. In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 1. In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is less than 1. In some embodiments, Y in the mutant can be a moiety comprising 10 to 50 amino acids, and a total number of Cysteine (C) of Y is 0.
[0281] In some embodiments, a total number of hydrophobic amino acids in Y in the mutant is more than 8. In some embodiments, a total number of hydrophobic amino acids in Y in the mutant is more than 9. In some embodiments, a total number of hydrophobic amino acids in Y in the mutant is more than 10. In some embodiments, a total number of hydrophobic amino acids in Y in the mutant is more than 11. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is more than 12. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is more than 13. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is more than 14. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is more than 15.
[0282] In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is 5. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is no more than 5. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is 4. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is no more than 4. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is 3. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is no more than 3. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is 2. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is no more than 2. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is 1. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is no more than 1.
[0283] In some embodiments, Y in the mutant comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence of any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the mutant is a sequence of any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85.
[0284] In some embodiments, Y in the mutant comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the mutant comprises a sequence of any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the mutant is a sequence of any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85.
[0285] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) , X-Y (II) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A, Y comprises a sequence having at most 90%identity with SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.
[0286] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) .
[0287] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) .
[0288] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) .
[0289] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) .
[0290] In some embodiments, at least 20%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H.
[0291] In some embodiments, X in the mutant comprises a sequence having at least 70%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 75%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 80%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 85%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 95%identity with SEQ ID NO: 1.
[0292] In some embodiments, Y in the mutant comprises a sequence having at most 50%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 55%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 60%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 65%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 70%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 75%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 80%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 85%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 90%identity with SEQ ID NO: 2.
[0293] In some embodiments, a total number of hydrophobic amino acids in Y in the mutant is more than 8. In some embodiments, a total number of hydrophobic amino acids in Y in the mutant is more than 9. In some embodiments, a total number of hydrophobic amino acids in Y in the mutant is more than 10. In some embodiments, a total number of hydrophobic amino acids in Y in the mutant is more than 11. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is more than 12. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is more than 13. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is more than 14. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is more than 15.
[0294] In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is 5. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is no more than 5. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is 4. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is no more than 4. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is 3. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is no more than 3. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is 2. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is no more than 2. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is 1. In some embodiments, a total number of hydrophilic amino acids in Y in the mutant is no more than 1.
[0295] In some embodiments, Y in the mutant comprises a sequence having at least 70%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y in the mutant comprises a sequence having at least 75%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y in the mutant comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y in the mutant comprises a sequence having at least 85%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y in the mutant comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y in the mutant comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y in the mutant comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NOs: 16-18. In some embodiments, Y in the mutant comprises a sequence of any one selected from SEQ ID NOs: 16-18. In some embodiments, Y in the mutant is a sequence of any one selected from SEQ ID NOs: 16-18.
[0296] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) , X-Y (III) , wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E, Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2, a total number of H, R, K, D, Q, N and E in X is less than 33, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.
[0297] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) .
[0298] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) .
[0299] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) .
[0300] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) .
[0301] In some embodiments, at least 20%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H.
[0302] In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 33. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 32. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 31. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 30. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 29. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 28. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 27.In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 26. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 25. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 24. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 23. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 22. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 21. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of H, R, K, D, Q, N and E in X is less than 20.
[0303] In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 10. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 11. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 12. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 13. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 14. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 15. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 16. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 17. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 18. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 19. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 20. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 21. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 22. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 23. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 24. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 25.
[0304] In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 15. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 14. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 13. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 12. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 11. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 10. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 5.
[0305] In some embodiments, X in the mutant comprises a sequence having at least 70%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 75%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 80%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 85%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 95%identity with SEQ ID NO: 1.
[0306] In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 70%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 75%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 85%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 90%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 95%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence of SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety that is a sequence of SEQ ID NO: 2.
[0307] In some embodiments, Y in the mutant is hydrophobic moiety, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 55%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 60%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 65%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 70%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 75%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 80%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 85%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 90%amino acids of Y are selected from I, V, L, F, C, M, and A.
[0308] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) , X-Y (IV) , wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E, Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2, X comprises a sequence having at most 90%identity with SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.
[0309] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) .
[0310] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) .
[0311] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) .
[0312] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) .
[0313] In some embodiments, at least 20%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H.
[0314] In some embodiments, X in the mutant comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 10. In some embodiments, X in the mutant comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 15. In some embodiments, X in the mutant comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 20. In some embodiments, X in the mutant comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 25. In some embodiments, X in the mutant comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 30. In some embodiments, X in the mutant comprises 40 to 65 amino acids, and a total number of hydrophilic amino acids in X is more than 35.
[0315] In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 15. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 14. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 13. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 12. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 11. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 10. In some embodiments, X in the mutant is a moiety comprising 40 to 65 amino acids, and a total number of hydrophobic amino acids in X is no more than 5.
[0316] In some embodiments, X in the mutant comprises a sequence having at least 70%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 75%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 80%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 85%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 95%identity with SEQ ID NO: 1.
[0317] In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 70%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 75%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 85%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 90%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 95%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety comprising a sequence of SEQ ID NO: 2. In some embodiments, Y in the mutant is a moiety that is a sequence of SEQ ID NO: 2.
[0318] In some embodiments, Y in the mutant is hydrophobic moiety, at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 55%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 60%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 65%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 70%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 75%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 80%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 85%amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is hydrophobic moiety, at least 90%amino acids of Y are selected from I, V, L, F, C, M, and A.
[0319] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) , X-Y (V) , wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.
[0320] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) .
[0321] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) .
[0322] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) .
[0323] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) .
[0324] In some embodiments, at least 20%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90%amino acids of X in the mutant are selected from R, K, N, D, Q, E, and H.
[0325] In some embodiments, Y in the mutant comprises 10 to 25 amino acids. In some embodiments, Y in the mutant comprises 10 to 20 amino acids. In some embodiments, Y in the mutant comprises 10 to 15 amino acids. In some embodiments, Y in the mutant comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 amino acids.
[0326] In some embodiments, X in the mutant comprises a sequence having at least 70%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 75%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 80%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 85%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 90%identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 95%identity with SEQ ID NO: 1.
[0327] In some embodiments, Y in the mutant comprises a sequence having at most 50%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 55%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 60%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 65%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 70%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 75%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 80%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 85%identity with SEQ ID NO: 2. In some embodiments, Y in the mutant comprises a sequence having at most 90%identity with SEQ ID NO: 2.
[0328] In another aspect, provided is a method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.
[0329] In another aspect, provided is a method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.
[0330] In another aspect, provided is a method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.
[0331] In another aspect, provided is a method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.
[0332] In another aspect, provided is a method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.
[0333] In some embodiments, the polypeptide has at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 75%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 80%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 85%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 90%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 95%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 96%, at least 97%, at least 98%, or at least 99%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide comprises or is an amino acid sequence of any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74. In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NOs: 28 and 62-74. In some embodiments, the polypeptide is a polypeptide of SEQ ID NO: 28.
[0334] In another aspect, provided is an artificial polypeptide of formula (I) , (II) , (III) , (IV) , (V) , (VI) , or (VII) , or a mutant of artificial polypeptide of (I) , (II) , (III) , (IV) or (V) , or a polypeptide having at least 70%identity with any one selected from SEQ ID NO. 28, SEQ ID NOs. 57 and 62-74 or a fragment or variant thereof, for use in preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, improving nerve conduction velocity in a subject in need thereof, increasing intraepidermal nerve fiber density in a subject in need thereof, or any combination thereof.
[0335] In another aspect, provided is use of an artificial polypeptide of formula (I) , (II) , (III) , (IV) , (V) , (VI) , or (VII) , or a mutant of artificial polypeptide of (I) , (II) , (III) , (IV) or (V) , or a polypeptide having at least 70%identity with any one selected from SEQ ID NO. 28, SEQ ID NOs. 57 and 62-74 or a fragment or variant thereof for the preparation of a medicament for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, improving nerve conduction velocity in a subject in need thereof, increasing intraepidermal nerve fiber density in a subject in need thereof, or any combination thereof.
[0336] In some embodiments, the medicament is a medicament for use in human.
[0337] In some embodiments, the medicament is a veterinary medicament.
[0338] In some embodiments of either of the above aspects, the subject is a mammal. In some embodiments, the subject is any one selected from the group consisting of a human, primate, rodent, canine, feline, equine, ovine and porcine. In some embodiments, the subject is a human. In some embodiments, the subject is an infant, a toddler, a child, an adolescent, an adult, or an elderly. In some embodiments, the subject is a man or a woman. In some embodiments, the subject is a pet. In some embodiments, the subject is any one selected from the group consisting of mice, rat, guinea pig, gerbil, hamster, chinchilla, rabbit, ferret, cat, dog and pig.
[0339] In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy. In some embodiments, the peripheral neuropathy is mononeuropathy. In some embodiments, the peripheral neuropathy is mononeuritis multiplex. In some embodiments, the peripheral neuropathy is polyneuropathy.
[0340] In some embodiments, the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy. In some embodiments, the peripheral neuropathy is motor neuropathy. In some embodiments, the peripheral neuropathy is sensory neuropathy. In some embodiments, the peripheral neuropathy is autonomic neuropathy.
[0341] In some embodiments, the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency. In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the peripheral neuropathy is associated with compression. In some embodiments, the peripheral neuropathy is associated with traumatic injury. In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the peripheral neuropathy is associated with exposure to toxic chemical agents. In some embodiments, the peripheral neuropathy is associated with radiation therapy. In some embodiments, the peripheral neuropathy is associated with excessive alcohol consumption. In some embodiments, the peripheral neuropathy is associated with vitamin deficiency.
[0342] In some embodiments, the peripheral neuropathy is associated with medical condition. In some embodiments, the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia. In some embodiments, the medical condition is inflammation. In some embodiments, the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis. In some embodiments, the medical condition is infection. In some embodiments, the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection. In some embodiments, the infection is viral infection. In some embodiments, the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection. In some embodiments, the medical condition is tumor. In some embodiments, the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma. In some embodiments, the medical condition is immune system disease. In some embodiments, the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.
[0343] In some embodiments, the peripheral neuropathy is associated with medication. In some embodiments, the medication is treatment with chemotherapeutic agent and / or antibiotic. In some embodiments, the medication is treatment with chemotherapeutic agent. In some embodiments, the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin. In some embodiments, the chemotherapeutic agent is platinum-based antineoplastic drug. In some embodiments, the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate. In some embodiments, the platinum-based antineoplastic drug is cisplatin. In some embodiments, the chemotherapeutic agent is microtubule inhibitor. In some embodiments, the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca ...
Claims
1.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) : X-Y (I) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A;wherein Y comprises a total number of Cysteine (C) of less than 5.2.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) : X-Y (I) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A;wherein Y comprises a total number of Cysteine (C) of less than 5.3.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) : X-Y (I) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A;wherein Y comprises a total number of Cysteine (C) of less than 5.4.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) : X-Y (I) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A;wherein Y comprises a total number of Cysteine (C) of less than 5.5.The method of claim 4, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.6.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I) : X-Y (I) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A;wherein Y comprises a total number of Cysteine (C) of less than 5.7.The method of any one of claims 1 to 6, wherein X comprises a sequence having at least 90%identity with SEQ ID NO: 1, X comprises a sequence having at least 95%identity with SEQ ID NO: 1, or X comprises a sequence of SEQ ID NO: 1.8.The method of any one of claims 1 to 7, wherein at least 50%amino acids of X are selected from R, K, N, D, Q, E, and H.9.The method of any one of claims 1 to 8, wherein Y comprises a total number of Cysteine (C) of less than 4, Y comprises a total number of Cysteine (C) of less than 3, or Y comprises a total number of Cysteine (C) of less than 2.10.The method of any one of claims 1 to 9, wherein a total number of hydrophobic amino acids in Y is more than 8, the total number of hydrophobic amino acids in Y is more than 12, the total number of hydrophobic amino acids in Y is more than 15, and / or a total number of hydrophilic amino acids in Y is no more than 5.11.The method of any one of claims 1 to 10, wherein X comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 81-83.12.The method of any one of claims 1 to 11, wherein Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85, or Y comprises a sequence having at least 90%identity with anyone selected from SEQ ID NOs: 3-18, 58-61 and 84-85.13.The method of any one of claims 1 to 12, wherein the polypeptide comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 29-41, 54-57, 75 and 91-95.14.The method of claim 1, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.15.The method of claim 1, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.16.The method of claim 1, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.17.The method of claim 1, wherein the peripheral neuropathy is associated with medical condition.18.The method of claim 17, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.19.The method of claim 18, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.20.The method of claim 18, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.21.The method of claim 20, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.22.The method of claim 18, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.23.The method of claim 18, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.24.The method of claim 1, wherein the peripheral neuropathy is associated with medication.25.The method of claim 24, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.26.The method of claim 25, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.27.The method of claim 26, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.28.The method of claim 26, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.29.The method of claim 28, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.30.The method of claim 28, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.31.The method of claim 26, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.32.The method of claim 26, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.33.The method of claim 26, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.34.The method of claim 25, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.35.The method of claim 1, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .36.The method of claim 1, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.37.The method of any one of claims 1 to 13, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.38.The method of any one of claims 1 to 13, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.39.The method of any one of claims 1 to 13, wherein the subject does not manifest peripheral neuropathic pain.40.The method of any one of claims 1 to 13, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.41.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) : X-Y (II) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A;wherein Y comprises a sequence having at most 90%identity with SEQ ID NO: 2.42.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) : X-Y (II) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A;wherein Y comprises a sequence having at most 90%identity with SEQ ID NO: 2.43.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) : X-Y (II) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A;wherein Y comprises a sequence having at most 90%identity with SEQ ID NO: 2.44.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) : X-Y (II) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A;wherein Y comprises a sequence having at most 90%identity with SEQ ID NO: 2.45.The method of claim 44, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.46.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II) : X-Y (II) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A;wherein Y comprises a sequence having at most 90%identity with SEQ ID NO: 2.47.The method of any one of claims 41 to 46, wherein X comprises a sequence having at least 90%identity with SEQ ID NO: 1, X comprises a sequence having at least 95%identity with SEQ ID NO: 1, or X comprises a sequence of SEQ ID NO: 1.48.The method of any one of claims 41 to 47, wherein at least 50%amino acids of X are selected from R, K, N, D, Q, E, and H.49.The method of any one of claims 41 to 48, wherein Y comprises a sequence having at most 80%identity with SEQ ID NO: 2, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2, or Y comprises a sequence having at most 50%identity with SEQ ID NO: 2.50.The method of any one of claims 41 to 49, wherein a total number of hydrophobic amino acids in Y is more than 8, the total number of hydrophobic amino acids in Y is more than 12, the total number of hydrophobic amino acids in Y is more than 15, and / or a total number of hydrophilic amino acids in Y is no more than 5.51.The method of any one of claims 41 to 50, wherein Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 16-18, or Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 16-18.52.The method of any one of claims 41 to 51, wherein the polypeptide comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 42-44.53.The method of claim 41, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.54.The method of claim 41, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.55.The method of claim 41, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.56.The method of claim 41, wherein the peripheral neuropathy is associated with medical condition.57.The method of claim 56, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.58.The method of claim 57, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.59.The method of claim 57, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.60.The method of claim 59, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.61.The method of claim 57, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.62.The method of claim 57, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.63.The method of claim 41, wherein the peripheral neuropathy is associated with medication.64.The method of claim 63, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.65.The method of claim 64, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.66.The method of claim 65, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.67.The method of claim 65, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.68.The method of claim 67, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.69.The method of claim 67, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.70.The method of claim 65, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.71.The method of claim 65, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.72.The method of claim 65, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.73.The method of claim 64, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.74.The method of claim 41, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .75.The method of claim 41, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.76.The method of any one of claims 41 to 52, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.77.The method of any one of claims 41 to 52, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.78.The method of any one of claims 41 to 52, wherein the subject does not manifest peripheral neuropathic pain.79.The method of any one of claims 41 to 52, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.80.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) : X-Y (III) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; andY is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,wherein a total number of H, R, K, D, Q, N and E in X is less than 33.81.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) : X-Y (III) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; andY is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,wherein a total number of H, R, K, D, Q, N and E in X is less than 33.82.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) : X-Y (III) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; andY is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,wherein a total number of H, R, K, D, Q, N and E in X is less than 33.83.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) : X-Y (III) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; andY is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,wherein a total number of H, R, K, D, Q, N and E in X is less than 33.84.The method of claim 83, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.85.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III) : X-Y (III) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; andY is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,wherein a total number of H, R, K, D, Q, N and E in X is less than 33.86.The method of any one of claims 80 to 85, wherein Y comprises a sequence having at least 90%identity with SEQ ID NO: 2, Y comprises a sequence having at least 95%identity with SEQ ID NO: 2, or Y comprises a sequence of SEQ ID NO: 2.87.The method of any one of claims 80 to 86, wherein at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A.88.The method of any one of claims 80 to 87, wherein the total number of H, R, K, D, Q, N and E in X is less than 30, the total number of H, R, K, D, Q, N and E in X is less than 25, or the total number of H, R, K, D, Q, N and E in X is less than 20.89.The method of any one of claims 80 to 88, wherein a total number of hydrophilic amino acids in X is more than 10, a total number of hydrophilic amino acids in X is more than 15, a total number of hydrophilic amino acids in X is more than 20, a total number of hydrophilic amino acids in X is more than 25, a total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10.90.The method of any one of claims 80 to 89, wherein X comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 23-27, or X comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 23-27.91.The method of any one of claims 80 to 90, wherein the polypeptide comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 49-53.92.The method of claim 80, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.93.The method of claim 80, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.94.The method of claim 80, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.95.The method of claim 80, wherein the peripheral neuropathy is associated with medical condition.96.The method of claim 95, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.97.The method of claim 96, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.98.The method of claim 96, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.99.The method of claim 98, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.100.The method of claim 96, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.101.The method of claim 96, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.102.The method of claim 80, wherein the peripheral neuropathy is associated with medication.103.The method of claim 102, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.104.The method of claim 103, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.105.The method of claim 104, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.106.The method of claim 104, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.107.The method of claim 106, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.108.The method of claim 106, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.109.The method of claim 104, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.110.The method of claim 104, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.111.The method of claim 104, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.112.The method of claim 103, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.113.The method of claim 80, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .114.The method of claim 80, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.115.The method of any one of claims 80 to 91, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.116.The method of any one of claims 80 to 91, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.117.The method of any one of claims 80 to 91, wherein the subject does not manifest peripheral neuropathic pain.118.The method of any one of claims 80 to 91, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.119.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) : X-Y (IV) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; andY is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,wherein X comprises a sequence having at most 90%identity with SEQ ID NO: 1.120.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) : X-Y (IV) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; andY is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,wherein X comprises a sequence having at most 90%identity with SEQ ID NO: 1.121.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) : X-Y (IV) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; andY is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,wherein X comprises a sequence having at most 90%identity with SEQ ID NO: 1.122.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) : X-Y (IV) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; andY is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,wherein X comprises a sequence having at most 90%identity with SEQ ID NO: 1.123.The method of claim 122, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.124.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV) : X-Y (IV) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E; andY is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,wherein X comprises a sequence having at most 90%identity with SEQ ID NO: 1.125.The method of any one of claims 119 to 124, wherein X comprises a sequence having at most 80%identity with SEQ ID NO: 1, X comprises a sequence having at most 70%identity with SEQ ID NO: 1, or X comprises a sequence having at most 50%identity with SEQ ID NO: 1.126.The method of any one of claims 119 to 125, wherein Y comprises a sequence having at least 90%identity with SEQ ID NO: 2, Y comprises a sequence having at least 95%identity with SEQ ID NO: 2, or Y comprises a sequence of SEQ ID NO: 2.127.The method of any one of claims 119 to 126, wherein at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A.128.The method of any one of claims 119 to 127, wherein a total number of hydrophilic amino acids in X is more than 10, a total number of hydrophilic amino acids in X is more than 15, a total number of hydrophilic amino acids in X is more than 20, a total number of hydrophilic amino acids in X is more than 25, a total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10.129.The method of any one of claims 119 to 128, wherein X comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 19-22 and 76-79, or X comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 19-22 and 76-79.130.The method of any one of claims 119 to 129, wherein the polypeptide comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 45-48 and 86-89.131.The method of claim 119, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.132.The method of claim 119, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.133.The method of claim 119, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.134.The method of claim 119, wherein the peripheral neuropathy is associated with medical condition.135.The method of claim 134, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.136.The method of claim 135, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.137.The method of claim 135, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.138.The method of claim 137, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.139.The method of claim 135, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.140.The method of claim 135, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.141.The method of claim 119, wherein the peripheral neuropathy is associated with medication.142.The method of claim 141, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.143.The method of claim 142, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.144.The method of claim 143, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.145.The method of claim 143, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.146.The method of claim 145, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.147.The method of claim 145, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.148.The method of claim 143, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.149.The method of claim 143, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.150.The method of claim 143, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.151.The method of claim 142, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.152.The method of claim 119, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .153.The method of claim 119, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.154.The method of any one of claims 119 to 130, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.155.The method of any one of claims 119 to 130, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.156.The method of any one of claims 119 to 130, wherein the subject does not manifest peripheral neuropathic pain.157.The method of any one of claims 119 to 130, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.158.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) : X-Y (V) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2.159.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) : X-Y (V) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2.160.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) : X-Y (V) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2.161.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) : X-Y (V) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2.162.The method of claim 161, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.163.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (V) : X-Y (V) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1, andY is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2.164.The method of any one of claims 158 to 163, wherein Y comprises 10 to 25 amino acids, Y comprises 10 to 20 amino acids, or Y comprises 10 to 15 amino acids.165.The method of any one of claims 158 to 164, wherein X comprises a sequence having at least 90%identity with SEQ ID NO: 1, X comprises a sequence having at least 95%identity with SEQ ID NO: 1, or X comprises a sequence of SEQ ID NO: 1.166.The method of any one of claims 158 to 165, wherein at least 50%amino acids of X are selected from R, K, N, D, Q, E, and H.167.The method of any one of claims 158 to 166, wherein X comprises a sequence having at least 80%identity with SEQ ID NO: 96, X comprises a sequence having at least 90%identity with SEQ ID NO: 96, X comprises a sequence having at least 95%identity with SEQ ID NO: 96, or X comprises a sequence of SEQ ID NO: 96.168.The method of any one of claims 158 to 167, wherein Y comprises a sequence having at most 80%identity with SEQ ID NO: 2, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2, or Y comprises a sequence having at most 50%identity with SEQ ID NO: 2.169.The method of any one of claims 158 to 168, wherein Y comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 97-103, Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 97-103, Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 97-103, or Y comprises a sequence that is any one selected from SEQ ID NOs: 97-103.170.The method of any one of claims 158 to 169, wherein the polypeptide comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 53-56 and 104-110.171.The method of claim 158, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.172.The method of claim 158, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.173.The method of claim 158, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.174.The method of claim 158, wherein the peripheral neuropathy is associated with medical condition.175.The method of claim 174, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.176.The method of claim 175, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.177.The method of claim 175, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.178.The method of claim 177, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.179.The method of claim 175, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.180.The method of claim 175, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.181.The method of claim 158, wherein the peripheral neuropathy is associated with medication.182.The method of claim 181, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.183.The method of claim 182, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.184.The method of claim 183, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.185.The method of claim 183, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.186.The method of claim 185, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.187.The method of claim 185, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.188.The method of claim 183, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.189.The method of claim 183, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.190.The method of claim 183, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.191.The method of claim 182, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.192.The method of claim 158, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .193.The method of claim 158, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.194.The method of any one of claims 158 to 170, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.195.The method of any one of claims 158 to 170, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.196.The method of any one of claims 158 to 170, wherein the subject does not manifest peripheral neuropathic pain.197.The method of any one of claims 158 to 170, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.198.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) : X-Y (VI) ,wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in SEQ ID NO: 1 mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in SEQ ID NO: 1 mutated to T; andY is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, or 5 C in SEQ ID NO: 2 mutated to A.199.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) : X-Y (VI) ,wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in SEQ ID NO: 1 mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in SEQ ID NO: 1 mutated to T; andY is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, or 5 C in SEQ ID NO: 2 mutated to A.200.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) : X-Y (VI) ,wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in SEQ ID NO: 1 mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in SEQ ID NO: 1 mutated to T; andY is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, or 5 C in SEQ ID NO: 2 mutated to A.201.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) : X-Y (VI) ,wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in SEQ ID NO: 1 mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in SEQ ID NO: 1 mutated to T; andY is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, or 5 C in SEQ ID NO: 2 mutated to A.202.The method of claim 201, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.203.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI) : X-Y (VI) ,wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in SEQ ID NO: 1 mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in SEQ ID NO: 1 mutated to T; andY is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, or 5 C in SEQ ID NO: 2 mutated to A.204.The method of any one of claims 198 to 203, wherein X comprises a sequence having at least 70%identity with SEQ ID NO: 1 and / or X comprises a sequence having at most 95%identity with SEQ ID NO: 1.205.The method of any one of claims 198 to 204, wherein Y comprises a sequence having at least 80%identity with SEQ ID NO: 2 and / or Y comprises a sequence having at most 95%identity with SEQ ID NO: 2.206.The method of any one of claims 198 to 205, wherein at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A.207.The method of any one of claims 198 to 206, wherein a total number of R, K, T, A, N, Q, D, E, S, and G in X is more than 30 and / or a total number of W, Y, F, M, L, I, and V in X is no more than 20.208.The method of any one of claims 198 to 207, wherein a total number of R, K, T, A, N, Q, D, E, S, and G in Y is more than 10 and / or a total number of W, Y, F, M, L, I, and V in Y is no more than 20.209.The method of any one of claims 198 to 208, wherein X comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 80-83, X comprises a sequence that is any one selected from SEQ ID NOs: 80-83, or X is a sequence that is any one selected from SEQ ID NOs: 80-83.210.The method of any one of claims 198 to 209, wherein Y comprises a sequence having at least 80%identity with SEQ ID NO: 3, Y comprises a sequence of SEQ ID NO: 3, or Y is a sequence of SEQ ID NO: 3.211.The method of any one of claims 198 to 210, wherein the artificial polypeptide comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 90-93, the artificial polypeptide comprises a sequence that is any one selected from SEQ ID NOs: 90-93, or the artificial polypeptide is a sequence that is any one selected from SEQ ID NOs: 90-93.212.The method of claim 198, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.213.The method of claim 198, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.214.The method of claim 198, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.215.The method of claim 198, wherein the peripheral neuropathy is associated with medical condition.216.The method of claim 215, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.217.The method of claim 216, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.218.The method of claim 216, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.219.The method of claim 218, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.220.The method of claim 216, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.221.The method of claim 216, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.222.The method of claim 198, wherein the peripheral neuropathy is associated with medication.223.The method of claim 222, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.224.The method of claim 223, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.225.The method of claim 224, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.226.The method of claim 224, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.227.The method of claim 226, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.228.The method of claim 226, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.229.The method of claim 224, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.230.The method of claim 224, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.231.The method of claim 224, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.232.The method of claim 223, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.233.The method of claim 198, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .234.The method of claim 198, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.235.The method of any one of claims 198 to 211, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.236.The method of any one of claims 198 to 211, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.237.The method of any one of claims 198 to 211, wherein the subject does not manifest peripheral neuropathic pain.238.The method of any one of claims 198 to 211, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.239.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) : X-Y (VII) ,wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1, andY is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 continuous AAs of SEQ ID NO: 2.240.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) : X-Y (VII) ,wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1, andY is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 continuous AAs of SEQ ID NO: 2.241.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) : X-Y (VII) ,wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1, andY is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 continuous AAs of SEQ ID NO: 2.242.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) : X-Y (VII) ,wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1, andY is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 continuous AAs of SEQ ID NO: 2.243.The method of claim 242, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.244.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII) : X-Y (VII) ,wherein X is a moiety comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1, andY is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 continuous AAs of SEQ ID NO: 2.245.The method of any one of claims 239 to 244, wherein the amino acid insertions are located at the N-terminal of X and / or the inserted amino acid is M.246.The method of any one of claims 239 to 245, wherein Y is a moiety comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations relative to SEQ ID NO: 2 and optionally the at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations are located at the C-terminal of Y.247.The method of any one of claims 239 to 246, wherein at least 50%amino acids of X are selected from R, K, N, D, Q, E, and H and / or at most 60%amino acids of X are selected from R, K, N, D, Q, E, and H.248.The method of any one of claims 239 to 247, wherein a total number of E or D in X is at least 8 and / or a total number of E or D in X is at most 15.249.The method of any one of claims 239 to 248, wherein a total number of R, K, T, A, N, Q, D, E, S, and G in X is more than 30 and / or a total number of W, Y, F, M, L, I, and V in X is no more than 20.250.The method of any one of claims 239 to 249, wherein Y comprises 15 to 25 amino acids, Y comprises 18 to 25 amino acids, or Y comprises 20 to 25 amino acids.251.The method of any one of claims 239 to 250, wherein 40-65%amino acids of Y are selected from I, V, L, F, C, M, and A.252.The method of any one of claims 239 to 251, wherein a total number of R, K, T, A, N, Q, D, E, S, and G in Y is no more than 10 and / or a total number of W, Y, F, M, L, I, and V in Y is no more than 15.253.The method of any one of claims 239 to 252, wherein X comprises a sequence having at least 80%identity with SEQ ID NO: 96, X comprises a sequence of SEQ ID NO: 96, or X is a sequence of SEQ ID NO: 96.254.The method of any one of claims 239 to 253, wherein Y comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 97-103, Y comprises a sequence that is any one selected from SEQ ID NOs: 97-103, or Y is a sequence that is any one selected from SEQ ID NOs: 97-103.255.The method of any one of claims 239 to 254, wherein the artificial polypeptide comprises a sequence having at least 80%identity with any one selected from SEQ ID NOs: 104-110, the artificial polypeptide comprises a sequence that is any one selected from SEQ ID NOs: 104-110, or the artificial polypeptide is a sequence that is any one selected from SEQ ID NOs: 104-110.256.The method of claim 239, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.257.The method of claim 239, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.258.The method of claim 239, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.259.The method of claim 239, wherein the peripheral neuropathy is associated with medical condition.260.The method of claim 259, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.261.The method of claim 260, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.262.The method of claim 260, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.263.The method of claim 262, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.264.The method of claim 260, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.265.The method of claim 260, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.266.The method of claim 239, wherein the peripheral neuropathy is associated with medication.267.The method of claim 266, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.268.The method of claim 267, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.269.The method of claim 268, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.270.The method of claim 268, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.271.The method of claim 270, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.272.The method of claim 270, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.273.The method of claim 268, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.274.The method of claim 268, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.275.The method of claim 268, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.276.The method of claim 267, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.277.The method of claim 239, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .278.The method of claim 239, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.279.The method of any one of claims 239 to 255, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.280.The method of any one of claims 239 to 255, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.281.The method of any one of claims 239 to 255, wherein the subject does not manifest peripheral neuropathic pain.282.The method of any one of claims 239 to 255, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.283.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) : X-Y (I) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A,Y comprises a total number of Cysteine (C) of less than 5,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.284.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) : X-Y (I) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A,Y comprises a total number of Cysteine (C) of less than 5,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.285.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) : X-Y (I) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A,Y comprises a total number of Cysteine (C) of less than 5,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.286.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) : X-Y (I) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A,Y comprises a total number of Cysteine (C) of less than 5,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.287.The method of claim 286, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.288.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (I) : X-Y (I) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A,Y comprises a total number of Cysteine (C) of less than 5,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.289.The method of any one of claims 283 to 288, wherein at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H, and / or at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H.290.The method of any one of claims 283 to 289, wherein X comprises a sequence having at least 70%identity with SEQ ID NO: 1.291.The method of any one of claims 283 to 290, wherein Y comprises a total number of Cysteine (C) of less than 4, or Y comprises a total number of Cysteine (C) of less than 3.292.The method of any one of claims 283 to 291, wherein a total number of hydrophobic amino acids in Y is more than 8, the total number of hydrophobic amino acids in Y is more than 12, the total number of hydrophobic amino acids in Y is more than 15, and / or a total number of hydrophilic amino acids in Y is no more than 5.293.The method of any one of claims 283 to 292, wherein Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85, or Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85.294.The method of claim 283, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.295.The method of claim 283, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.296.The method of claim 283, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.297.The method claim 283, wherein the peripheral neuropathy is associated with medical condition.298.The method of claim 297, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.299.The method of claim 298, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.300.The method of claim 298, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.301.The method of claim 300, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.302.The method of claim 298, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.303.The method of claim 298, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.304.The method of claim 283, wherein the peripheral neuropathy is associated with medication.305.The method of claim 304, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.306.The method of claim 305, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.307.The method of claim 306, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.308.The method of claim 306, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.309.The method of claim 308, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.310.The method of claim 308, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.311.The method of claim 306, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.312.The method of claim 306, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.313.The method of claim 306, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.314.The method of claim 305, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.315.The method of claim 283, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .316.The method of claim 283, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.317.The method of any one of claims 283 to 293, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.318.The method of any one of claims 283 to 293, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.319.The method of any one of claims 283 to 293, wherein the subject does not manifest peripheral neuropathic pain.320.The method of any one of claims 283 to 293, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.321.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) : X-Y (II) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A,Y comprises a sequence having at most 90%identity with SEQ ID NO: 2,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.322.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) : X-Y (II) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A,Y comprises a sequence having at most 90%identity with SEQ ID NO: 2,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.323.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) : X-Y (II) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A,Y comprises a sequence having at most 90%identity with SEQ ID NO: 2,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.324.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) : X-Y (II) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A,Y comprises a sequence having at most 90%identity with SEQ ID NO: 2,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.325.The method of claim 324, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.326.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (II) : X-Y (II) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 50 amino acids, at least 50%of which are selected from I, V, L, F, C, M, and A,Y comprises a sequence having at most 90%identity with SEQ ID NO: 2,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.327.The method of any one of claims 321 to 326, wherein at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H, and / or at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H.328.The method of any one of claims 321 to 327, wherein X comprises a sequence having at least 70%identity with SEQ ID NO: 1.329.The method of any one of claims 321 to 328, wherein Y comprises a sequence having at most 80%identity with SEQ ID NO: 2, or Y comprises a sequence having at most 70%identity with SEQ ID NO: 2.330.The method of any one of claims 321 to 329, wherein a total number of hydrophobic amino acids in Y is more than 8, the total number of hydrophobic amino acids in Y is more than 12, the total number of hydrophobic amino acids in Y is more than 15, and / or a total number of hydrophilic amino acids in Y is no more than 5.331.The method of any one of claims 321 to 330, wherein Y comprises a sequence having at least 90%identity with any one selected from SEQ ID NOs: 16-18, or Y comprises a sequence having at least 95%identity with any one selected from SEQ ID NOs: 16-18.332.The method of claim 321, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.333.The method of claim 321, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.334.The method of claim 321, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.335.The method of claim 321, wherein the peripheral neuropathy is associated with medical condition.336.The method of claim 335, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.337.The method of claim 336, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.338.The method of claim 336, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.339.The method of claim 338, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.340.The method of claim 336, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.341.The method of claim 336, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.342.The method of claim 321, wherein the peripheral neuropathy is associated with medication.343.The method of claim 342, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.344.The method of claim 343, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.345.The method of claim 344, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.346.The method of claim 344, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.347.The method of claim 346, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.348.The method of claim 346, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.349.The method of claim 344, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.350.The method of claim 344, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.351.The method of claim 344, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.352.The method of claim 343, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.353.The method of claim 321, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .354.The method of claim 321, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.355.The method of any one of claims 321 to 331, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.356.The method of any one of claims 321 to 331, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.357.The method of any one of claims 321 to 331, wherein the subject does not manifest peripheral neuropathic pain.358.The method of any one of claims 321 to 331, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.359.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) : X-Y (III) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E,Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,a total number of H, R, K, D, Q, N and E in X is less than 33,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.360.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) : X-Y (III) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E,Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,a total number of H, R, K, D, Q, N and E in X is less than 33,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.361.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) : X-Y (III) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E,Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,a total number of H, R, K, D, Q, N and E in X is less than 33,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.362.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) : X-Y (III) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E,Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,a total number of H, R, K, D, Q, N and E in X is less than 33,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.363.The method of claim 362, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.364.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (III) : X-Y (III) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E,Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,a total number of H, R, K, D, Q, N and E in X is less than 33,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.365.The method of any one of claims 359 to 364, wherein at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H, and / or at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H.366.The method of any one of claims 359 to 365, wherein X comprises a sequence having at least 70%identity with SEQ ID NO: 1.367.The method of any one of claims 359 to 366, wherein Y comprises a sequence having at least 90%identity with SEQ ID NO: 2, or Y comprises a sequence of SEQ ID NO: 2.368.The method of any one of claims 359 to 367, wherein at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A.369.The method of any one of claims 359 to 368, wherein the total number of H, R, K, D, Q, N and E in X is less than 30, the total number of H, R, K, D, Q, N and E in X is less than 25, or the total number of H, R, K, D, Q, N and E in X is less than 20.370.The method of any one of claims 359 to 369, wherein a total number of hydrophilic amino acids in X is more than 10, a total number of hydrophilic amino acids in X is more than 15, a total number of hydrophilic amino acids in X is more than 20, a total number of hydrophilic amino acids in X is more than 25, a total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10.371.The method of claim 359, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.372.The method of claim 359, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.373.The method of claim 359, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.374.The method of claim 359, wherein the peripheral neuropathy is associated with medical condition.375.The method of claim 374, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.376.The method of claim 375, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.377.The method of claim 375, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.378.The method of claim 377, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.379.The method of claim 375, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.380.The method of claim 375, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.381.The method of claim 359, wherein the peripheral neuropathy is associated with medication.382.The method of claim 381, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.383.The method of claim 382, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.384.The method of claim 383, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.385.The method of claim 383, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.386.The method of claim 385, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.387.The method of claim 385, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.388.The method of claim 383, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.389.The method of claim 383, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.390.The method of claim 383, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.391.The method of claim 382, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.392.The method of claim 359, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .393.The method of claim 359, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.394.The method of any one of claims 359 to 370, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.395.The method of any one of claims 359 to 370, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.396.The method of any one of claims 359 to 370, wherein the subject does not manifest peripheral neuropathic pain.397.The method of any one of claims 359 to 370, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.398.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) : X-Y (IV) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E,Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,X comprises a sequence having at most 90%identity with SEQ ID NO: 1,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.399.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) : X-Y (IV) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E,Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,X comprises a sequence having at most 90%identity with SEQ ID NO: 1,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.400.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) : X-Y (IV) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E,Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,X comprises a sequence having at most 90%identity with SEQ ID NO: 1,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.401.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) : X-Y (IV) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E,Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,X comprises a sequence having at most 90%identity with SEQ ID NO: 1,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.402.The method of claim 401, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.403.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (IV) : X-Y (IV) ,wherein X is a moiety comprising 40 to 65 amino acids, at least 50%of which are selected from H, R, K, D, Q, N and E,Y is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 2,X comprises a sequence having at most 90%identity with SEQ ID NO: 1,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.404.The method of any one of claims 398 to 403, wherein at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H, and / or at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H.405.The method of any one of claims 398 to 404, wherein X comprises a sequence having at least 70%identity with SEQ ID NO: 1.406.The method of any one of claims 398 to 405, wherein Y comprises a sequence having at least 90%identity with SEQ ID NO: 2, or Y comprises a sequence of SEQ ID NO: 2.407.The method of any one of claims 398 to 406, wherein at least 50%amino acids of Y are selected from I, V, L, F, C, M, and A.408.The method of any one of claims 398 to 407, wherein a total number of hydrophilic amino acids in X is more than 10, a total number of hydrophilic amino acids in X is more than 15, a total number of hydrophilic amino acids in X is more than 20, a total number of hydrophilic amino acids in X is more than 25, a total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10.409.The method of claim 398, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.410.The method of claim 398, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.411.The method of claim 398, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.412.The method of claim 398, wherein the peripheral neuropathy is associated with medical condition.413.The method of claim 412, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.414.The method of claim 413, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.415.The method of claim 413, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.416.The method of claim 415, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.417.The method of claim 413, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.418.The method of claim 413, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.419.The method of claim 398, wherein the peripheral neuropathy is associated with medication.420.The method of claim 419, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.421.The method of claim 420, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.422.The method of claim 421, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.423.The method of claim 421, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.424.The method of claim 423, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.425.The method of claim 423, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.426.The method of claim 421, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.427.The method of claim 421, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.428.The method of claim 421, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.429.The method of claim 420, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.430.The method of claim 398, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .431.The method of claim 398, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.432.The method of any one of claims 398 to 408, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.433.The method of any one of claims 398 to 408, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.434.The method of any one of claims 398 to 408, wherein the subject does not manifest peripheral neuropathic pain.435.The method of any one of claims 398 to 408, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.436.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) : X-Y (V) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.437.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) : X-Y (V) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.438.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) : X-Y (V) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.439.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) : X-Y (V) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.440.The method of claim 439, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.441.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of artificial polypeptide of formula (V) : X-Y (V) ,wherein X is a moiety comprising a sequence having at least 80%identity with SEQ ID NO: 1,Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 continuous AAs of SEQ ID NO: 2,characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.442.The method of any one of claims 436 to 441, wherein at least 20%amino acids of X are selected from R, K, N, D, Q, E, and H, at least 30%amino acids of X are selected from R, K, N, D, Q, E, and H, at most 90%amino acids of X are selected from R, K, N, D, Q, E, and H, and / or at most 80%amino acids of X are selected from R, K, N, D, Q, E, and H.443.The method of any one of claims 436 to 442, wherein Y comprises 10 to 25 amino acids, Y comprises 10 to 20 amino acids, or Y comprises 10 to 15 amino acids.444.The method of any one of claims 436 to 443, wherein X comprises a sequence having at least 70%identity with SEQ ID NO: 1.445.The method of any one of claims 436 to 444, wherein Y comprises a sequence having at most 80%identity with SEQ ID NO: 2, Y comprises a sequence having at most 70%identity with SEQ ID NO: 2, or Y comprises a sequence having at most 50%identity with SEQ ID NO: 2.446.The method of claim 436, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.447.The method of claim 436, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.448.The method of claim 436, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.449.The method of claim 436, wherein the peripheral neuropathy is associated with medical condition.450.The method of claim 449, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.451.The method of claim 450, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.452.The method of claim 450, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.453.The method of claim 452, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.454.The method of claim 450, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.455.The method of claim 450, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.456.The method of claim 436, wherein the peripheral neuropathy is associated with medication.457.The method of claim 456, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.458.The method of claim 457, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.459.The method of claim 458, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.460.The method of claim 458, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.461.The method of claim 460, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.462.The method of claim 460, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.463.The method of claim 458, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.464.The method of claim 458, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.465.The method of claim 458, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.466.The method of claim 457, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.467.The method of claim 436, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .468.The method of claim 436, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.469.The method of any one of claims 436 to 445, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.470.The method of any one of claims 436 to 445, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.471.The method of any one of claims 436 to 445, wherein the subject does not manifest peripheral neuropathic pain.472.The method of any one of claims 436 to 445, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness; muscle atrophy; muscle twitches; cramps; and muscle paralysis.473.A method for preventing and / or treating peripheral neuropathy or nerve injury associated with peripheral neuropathy in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.474.A method for effecting and / or promoting neuroprotection and / or neuroregeneration in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.475.A method for alleviating and / or mitigating cell damage and / or inflammatory response of nervous tissues or nerve cells in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.476.A method for improving nerve conduction velocity in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.477.The method of claim 476, wherein the nerve conduction velocity is motor conduction velocity, sensory conduction velocity or both.478.A method for increasing intraepidermal nerve fiber density in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70%identity with any one selected from SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof.479.The method of any one of claims 473 to 478, wherein the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74 or a fragment or variant thereof, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NOs: 57 and 62-74, the polypeptide is a polypeptide of any one of SEQ ID NOs: 28 and 62-74, or the polypeptide is a polypeptide of SEQ ID NO: 28.480.The method of claim 473, wherein the peripheral neuropathy is one or more selected from the group consisting of mononeuropathy, mononeuritis multiplex and polyneuropathy.481.The method of claim 473, wherein the peripheral neuropathy is one or more selected from the group consisting of motor neuropathy, sensory neuropathy and autonomic neuropathy.482.The method of claim 473, wherein the peripheral neuropathy is associated with one or more selected from the group consisting of medical condition, compression, traumatic injury, medication, exposure to toxic chemical agents, radiation therapy, excessive alcohol consumption and vitamin deficiency.483.The method of claim 473, wherein the peripheral neuropathy is associated with medical condition.484.The method of claim 483, wherein the medical condition is one or more selected from the group consisting of diabetes, inflammation, amyotrophic lateral sclerosis (ALS) , spinal muscular atrophy (SMA) , post-polio syndrome, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) , multifocal motor neuropathy, muscular dystrophy, peripheral nerve injury, demyelination, adrenoleukodystrophy, kidney disease, liver disease, Parkinson's disease, stroke, Alzheimer's disease, infection, tumor, carpal tunnel syndrome, post-herpetic neuralgia, peroneal muscular atrophy, Fabry disease, severe polyneuropathy, Bell's palsy, ulnar nerve palsy, peroneal nerve palsy, ischemia, immune system disease, non-celiac gluten sensitivity, sarcoidosis and cryoglobulinemia.485.The method of claim 484, wherein the inflammation is one or more selected from the group consisting of acute disseminated leukoencephalitis, progressive multifocal leukoencephalitis (PML) , optic neuritis, transverse myelitis and vasculitis.486.The method of claim 484, wherein the infection is one or more selected from the group consisting of leprosy, lyme disease and viral infection.487.The method of claim 486, wherein the viral infection is one or more selected from the group consisting of parvovirus B19 infection and HIV infection.488.The method of claim 484, wherein the tumor is one or more selected from the group consisting of lymphoma, neurilemmoma and multiple myeloma.489.The method of claim 484, wherein the immune system disease is one or more selected from the group consisting of systemic lupus erythematosus (SLE) , rheumatoid arthritis and celiac disease.490.The method of of claim 473, wherein the peripheral neuropathy is associated with medication.491.The method of claim 490, wherein the medication is treatment with chemotherapeutic agent and / or antibiotic.492.The method of claim 491, wherein the chemotherapeutic agent is one or more selected from the group consisting of platinum-based antineoplastic drug, microtubule inhibitor, topoisomerase II inhibitor, immunomodulator, proteasome inhibitor and suramin.493.The method of claim 492, wherein the platinum-based antineoplastic drug is one or more selected from the group consisting of cisplatin, oxaliplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, eptaplatin, miriplatin, picoplatin, satraplatin and triplatin tetranitrate.494.The method of claim 492, wherein the microtubule inhibitor is one or more selected from the group consisting of taxoid, Vinca alkaloid, ixabepilone and eribulin.495.The method of claim 494, wherein the taxoid is one or more selected from the group consisting of paclitaxel, docetaxel and cabazitaxel.496.The method of claim 494, wherein the Vinca alkaloid is one or more selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine, vincaminol, vineridine and vinburnine.497.The method of claim 492, wherein the Topoisomerase II inhibitor is one or more selected from the group consisting of etoposide, teniposide, doxorubicin, daunorubicin, epirubicin and idarubicin.498.The method of claim 492, wherein the immunomodulator is one or more selected from the group consisting of thalidomide, lenalidomide and pomalidomide.499.The method of claim 492, wherein the proteasome inhibitor is one or more selected from the group consisting of bortezomib, carfilzomib, ixazomib, marizomib, oprozomib and delanzomib.500.The method of claim 491, wherein the antibiotic is one or more selected from the group consisting of metronidazole, ciprofloxacin, levofloxacin and moxifloxacin.501.The method of claim 473, wherein the peripheral neuropathy is diabetic peripheral neuropathy or chemotherapy-induced peripheral neuropathy (CIPN) .502.The method of claim 473, wherein the nerve injury associated with peripheral neuropathy is one or more selected from the group consisting of impaired nerve cells, impaired nerve fibers and impaired nerve conduction.503.The method of any one of claims 473 to 479, wherein the subject is afflicted by peripheral neuropathy or is in the risk of developing peripheral neuropathy.504.The method of any one of claims 473 to 479, wherein the subject does not manifest pain attributable to peripheral neuropathy or nerve injury associated with peripheral neuropathy.505.The method of any one of claims 473 to 479, wherein the subject does not manifest peripheral neuropathic pain.506.The method of any one of claims 473 to 479, wherein the subject manifests or is in the risk of developing one or more symptoms associated with peripheral neuropathy, wherein the symptoms associated with peripheral neuropathy are selected from the group consisting of inability to feel heat, cold and / or physical damage; numbness; hypersensitivity to touch; loss of coordination and / or proprioception; muscle weakness;muscle atrophy;muscle twitches;cramps;and muscle paralysis.
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