A pharmaceutical composition for treating parkinsonism

Abstract

The present application belongs to the technical field of biological medicine, and particularly relates to a pharmaceutical composition for treating Parkinson syndrome. Researches show that the Antarctic fish protein and the multi-domain derivative thereof have the functions of reducing PD pathology and protecting dopaminergic neurons.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a pharmaceutical composition for treating Parkinson's syndrome. Background Technology

[0002] Parkinson's disease (PD) is the second most common central neurodegenerative disease in the elderly, after Alzheimer's disease. PD primarily affects middle-aged and elderly individuals, and its incidence is increasing with the aging population. Currently, the cause of this disease is unknown, and it is incurable, posing a serious threat to human health and imposing a huge economic burden. Its pathological feature is the aggregation of α-synuclein in multiple nervous and peripheral systems, but its distribution and type vary, and it may also be influenced by other pathologies or cause similar manifestations. Previously, the disease was mainly considered a motor disorder, with typical features including resting tremor, bradykinesia, postural instability, and rigidity in the neck, trunk, and limbs. However, PD is now considered a disease with significant neuroinflammatory and immune dysfunction. Almost all Parkinsonian syndromes are influenced by genetic factors. More than 100 genes or gene loci have been identified, and most cases are likely caused by the interaction of multiple common and rare genetic variations. These genetic variations involve pathogenic genes for early-onset and late-onset Parkinson's syndromes, such as PARKIN, PINK1, DJ-1, SNCA, and LRRK2, as well as some susceptibility genes, such as GBA, TMEM175, GAK, and HTRA2.

[0003] Genetic research has revealed several unifying biological themes, including synaptic, lysosomal, mitochondrial, and immune-mediated mechanisms. These mechanisms interact and regulate, influencing neuronal function and survival. For example, α-synuclein can affect synaptic release, mitochondrial respiration, lysosomal degradation, and inflammatory responses, while LRRK2 can regulate lysosomal function, mitochondrial dynamics, autophagy, and immune signaling. Due to the heterogeneity of Parkinson's syndrome, more biomarkers are needed to diagnose, stratify, monitor, and predict disease progression and treatment response. Currently, some biomarkers are already in clinical or research use, such as α-synuclein in cerebrospinal fluid, dopamine transporters in neuroimaging, and neuron-specific enolases. Furthermore, several targeted therapies are under development, such as inhibiting α-synuclein accumulation, improving mitochondrial function, activating lysosomal enzymes, and regulating LRRK2 activity.

[0004] Numerous studies have shown that antifreeze proteins in Antarctic fish can protect plants and animals from cryogenic stress, including protecting cell membrane integrity, regulating ion balance (including calcium and potassium ions), and modulating ROS levels. Research indicates that Antarctic antifreeze proteins can also maintain intracellular ATP levels and enhance cell viability. ATP metabolism is also closely related to brain activity, and lower neuronal activity is associated with lower energy expenditure. The inhibition of ion currents by antifreeze proteins affects neuronal function, such as the generation of action potentials, synaptic transmission, and potential neuroprotective effects under conditions of excessive ion movement, such as brain hypoxia / ischemia and cold / reheat injury. Further research has shown that AFP I has the ability to reversibly inhibit neural network activity without affecting neuronal viability, playing a protective role during the hypothermia-rewarming process of hippocampal neurons. This cellular protective effect may be related to the inhibitory effect of AFP I, which may provide a neuroprotective mechanism—due to the lack of energy expenditure, intracellular ATP levels are maintained, allowing neurons to survive better during cold and rewarming processes.

[0005] In our previous studies, we found that in the Antarctic fish genome, the PD-causing gene α-syn is adjacent to the AFPIII gene, indicating that there may be a certain regulatory relationship between AFPIII and α-syn. Summary of the Invention

[0006] This invention demonstrates that Antarctic fish proteins and their multi-domain derivatives can alleviate PD pathology and protect dopaminergic neurons, thus completing this invention.

[0007] In a first aspect, the present invention provides a pharmaceutical composition for treating Parkinson's syndrome, the pharmaceutical composition comprising Antarctic fish protein and its derivatives, wherein the Antarctic fish protein is selected from one or more of CYN-1, CYN-2, CYN-3 and CYN-4 proteins, the nucleotide sequences of the CYN-1, CYN-2, CYN-3 and CYN-4 proteins are shown as SEQ ID NO: 1 to SEQ ID NO: 4 respectively, and their amino acid sequences are shown as SEQ ID NO: 5 to SEQ ID NO: 8 respectively, wherein;

[0008] The nucleotide sequences of CYN-1 to CYN-4 are as follows:

[0009] CYN-1SEQ ID NO: 1

[0010] ATGAAGTCAGTTGTTTTAACTGGTTTGCTGTTCGTCCTCGCTTGTGTCGAGCACATGAGTACAGCCAACAAGGCGTCCGTGGTGGCCAACCAGCTGATCCCCGTAAATACTGCCCTGACTCTGATAATGATGAAGGCGAAGGCGGTCACCCCAATGGGCCTCCCCGCCGAGGAAATTCCCCGAATAATCGGAATGCAAGCGAACAAGGCAGTGCCGTTGGGCACAACCCTCATGCCAGACATGATCAAAAACTATGAGTAG

[0011] CYN-2SEQ ID NO:2

[0012] ATGAAGTCAGTTGTTTTAACTGGTTTGCTGTTCGTCCTCGCTTGTGTCGAGCACATGAGTACAGCCAACAAGGCGTCCGTGGTGGCCAACCAGCTGATCCCCGTAAATACTGCCCTGACTCTGATAATGATGAAGGCGAAGGCGGTCACCCCAATGGGCCTCCCCGCCGAGGAAATTCCCCGAATAATCGGAATGCAAGCGAACAAGGCAGTGCCGTTGGGCACAACCCTCATGCCAGACATGATCAAAAACTATGAGGATGTGACGACATGTCCAGGCTTTAAGTCCGTGGTGGCCAACCAGCTGATCCCCATAAATACTGCCCTGACTCTAGTGATGATGAAGGCGGAGGCGGTCAGCCCAAAGGGCCTCCCTGCCGAGGAAATCTCCAAACTAGTGGGAATGCAAGCGAACAAGGCAGTGTATCTGGACCAAACCCTCATGCCAGATATGATCAAAAACTATGAGTAG

[0013] CYN-3 SEQ ID NO:3

[0014] ATGAAGTCAGTTGTTTTAACTGGTTTGCTGTTCGTCCTCGCTTGTGTCGAGCACATGAGTACAGCCAACAAGGCGTCCGTGGTGGCCAACCAGCTGATCCCCGTAAATACTGCCCTGACTCTGATAATGATGAAGGCGAAGGCGGTCACCCCAATGGGCCTCCCCGCCGAGGAAATTCCCCGAATAATCGGAATGCAAGCGAACAAGGCAGTGCCGTTGGGCACAACCCTCATGCCAGACATGATCAAAAACTATGAGGATGTGACGACATGTCCAGGCTTTAAGTCCGTGGTGGCCAACCAGCTGATCCCCATAAATACTGCCCTGACTCTAGTGATGATGAAGGCGGAGGCGGTCAGCCCAAAGGGCCTCCCTGCCGAGGAAATCTCCAAACTAGTGGGAATGCAAGCGAACAAGGCAGTGTATCTGGACCAAACCCTCATGCCAGATATGATCAAAAACTATGAGGATGGGACGACATGTCCAGGCATTAAGTCCGTGGTGGCCAACCAGCTGATCCCCATAAATACTGCCCTGACTCTAGTGATGATGAAGGCGGAGGCGGTCAGCCCAAAGGGCCTCCCTGCCGAGGAACTCCCCAAACTAGTGGGAATGCAAGCGAACAAGGCAGTGTATCTGGACCAAACCCTCATGCCAGATATGATCAAAAACTATGAGTAG

[0015] CYN-4 SEQ ID NO:4

[0016] ATGAAGTCAGTTGTTTTAACTGGTTTGCTGTTCGTCCTCGCTTGTGTCGAGCACATGAGTACAGCCAACAAGGCGTCCGTGGTGGCCAACCAGCTGATCCCCGTAAATACTGCCCTGACTCTGATAATGATGAAGGCGAAGGCGGTCACCCCAATGGGCCTCCCCGCCGAGGAAATTCCCCGAATAATCGGAATGCAAGCGAACAAGGCAGTGCCGTTGGGCACAACCCTCATGCCAGACATGATCAAAAACTATGAGGATGTGACGACATGTCCAGGCTTTAAGTCCGTGGTGGCCAACCAGCTGATCCCCATAAATACTGCCCTGACTCTAGTGATGATGAAGGCGGAGGCGGTCAGCCCAAAGGGCCTCCCTGCCGAGGAAATCTCCAAACTAGTGGGAATGCAAGCGAACAAGGCAGTGTATCTGGACCAAACCCTCATGCCAGATATGATCAAAAACTATGAGGATGGGACGACATGTCCAGGCATTAAGTCCGTGGTGGCCAACCAGCTGATCCCCATAAATACTGCCCTGACTCTAGTGATGATGAAGGCGGAGGCGGTCAGCCCAAAGGGCCTCCCTGCCGAGGAACTCCCCAAACTAGTGGGAATGCAAGCGAACAAGGCAGTGTATCTGGACCAAACCCTCATGCCAGATATGATCAAAAACTATGAGGATGGGACGACATGTCCAGGCATTAAGTCCGTGGTGGCCAACCAGCTGATCCCCATAAATACTGCCCTGACTCTAGTGATGATGAAGGCGGAGGCGGTCAGCCCAAAGGGCCTCCCTGCCGAGGAACTCCCCAAACTAGTGGGAATGCAAGCGAACAAGGCAGTGTATCTGGACGAAACCCTCATGCCAGATATGATCAAAAACTATGAGTAG

[0017] The amino acid sequences of CYN-1 to CYN-4 are as follows:

[0018] CYN-1SEQ ID NO: 5

[0019] MKSVVLTGLLFVLACVEHMSTANKASVVANQLIPVNTALTLIMMKAKAVTPMGLPAEEIPRIIGMQANKAVPLGTTLMPDMIKNYE

[0020] CYN-2SEQ ID NO: 6

[0021] MKSVVLTGLLFVLACVEHMSTANKASVVANQLIPVNTALTLIMMKAKAVTPMGLPAEEIPRIIGMQANKAVPLGTTLMPDMIKNYEDVTTCPGFKSVVANQLIPINTALTLVMMKAEAVSPKGLPAEEISKLVGMQANKAVYLDQTLMPDMIKNYE

[0022] CYN-3SEQ ID NO: 7

[0023] MKSVVLTGLLFVLACVEHMSTANKASVVANQLIPVNTALTLIMMKAKAVTPMGLPAEEIPRIIGMQANKAVPLGTTLMPDMIKNYEDVTTPGFKSVVANQLIPINTALTLVMMKAEAVSPKGLPAEISKLVGMQANKAVYLDQTLMPDMIKNYEDGTTPPGIKSVVANQLIPINTALTLVMMKAEAVSPKGLPAEEIIPE

[0024] CYN-4SEQ ID NO: 8

[0025] MKSVVLTGLLFVLACVEHMSTANKASVVANQLIPVNTALTLIMMKAKAVTPMGLPAEEIPRIIGMQANKAVPLGTTLMPDMIKNYEDVTTPGFKSVVANQLIPINTALTLVMMKAEAVSPKGLPAEISKLVGMQANKAVYLDQTLMPDMIKNYEDGTTCPGIKKSVVANQLIPINTALTLVMMKAEAVSPKGLPAEEIIP

[0026] The derivatives of the CYN-1, CYN-2, CYN-3, and CYN-4 proteins refer to those having at least 80% homology with the amino acid sequences SEQ ID NO: 5-8 of the proteins, more preferably at least 85% homology; more preferably at least 90% homology; more preferably at least 95% homology; more preferably at least 97% homology; more preferably at least 98% homology; and more preferably at least 99% homology.

[0027] Furthermore, the derivatives of the CYN-1, CYN-2, CYN-3, and CYN-4 proteins refer to those with deletions, additions, and / or mutations of 1-50 amino acids in the amino acid sequences SEQ ID NO: 5-8 of the proteins, wherein the deletions, additions, and / or mutations may be continuous or discontinuous. Furthermore, the number of deleted, added, and / or mutated amino acids can be 1-40, 1-35, 1-30, 1-25, 1-20, 1-15, 1-10, 1-5, 2, 3, 4, or 5.

[0028] Furthermore, the Antarctic fish protein is preferably CYN-4 protein.

[0029] Furthermore, the pharmaceutical composition also contains other active ingredients, which are drugs that are different from the Antarctic fish protein and can promote the improvement and / or treatment of Parkinson's syndrome symptoms.

[0030] Furthermore, the pharmaceutical composition can be prepared as sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, lozenges, granules, powders, pills, boluses, suspensions, powders, tinctures, preparations, drops, injections, powder injections, creams, sustained-release agents, targeted agents, etc.

[0031] Furthermore, the drug composition can be administered orally, by injection, implantation, external application, spraying, or inhalation.

[0032] In a second aspect, the present invention provides the application of Antarctic fish protein in the preparation of a drug for treating Parkinson's syndrome, wherein the Antarctic fish protein is selected from one or more of CYN-1, CYN-2, CYN-3 and CYN-4 proteins, the nucleotide sequences of the CYN-1, CYN-2, CYN-3 and CYN-4 proteins are shown as SEQ ID NO: 1 to SEQ ID NO: 4, and their amino acid sequences are shown as SEQ ID NO: 5 to SEQ ID NO: 8, respectively;

[0033] Wherein, the derivatives of the CYN-1, CYN-2, CYN-3 and CYN-4 proteins refer to those having at least 80% homology with the amino acid sequence SEQ ID NO: 5-8 of the proteins, more preferably at least 85% homology; more preferably at least 90% homology; more preferably at least 95% homology; more preferably at least 97% homology; more preferably at least 98% homology; more preferably at least 99% homology.

[0034] Furthermore, the derivatives of the CYN-1, CYN-2, CYN-3, and CYN-4 proteins refer to those with deletions, additions, and / or mutations of 1-50 amino acids in the amino acid sequences SEQ ID NO: 5-8 of the proteins, wherein the deletions, additions, and / or mutations may be continuous or discontinuous. Furthermore, the number of deleted, added, and / or mutated amino acids can be 1-40, 1-35, 1-30, 1-25, 1-20, 1-15, 1-10, 1-5, 2, 3, 4, or 5.

[0035] Furthermore, the Antarctic fish protein and its derivatives can reduce the phosphorylation level and aggregation of α-Syn in patients with Parkinson's syndrome.

[0036] Furthermore, the Antarctic fish protein and its derivatives can reduce TH cell damage in patients with Parkinson's syndrome. Attached Figure Description

[0037] Figure 1 Antarctic fish CYN protein reduces the phosphorylation level and aggregation of α-Syn in A53T cells (A. Antarctic fish CYN protein expression plasmid map; B. Antarctic fish CYN overexpression A53T cells pSyn immunofluorescence staining; C. Quantitative statistics of pSyn aggregation sites in cells).

[0038] Figure 2 Antarctic fish CYN-1 and CYN-4 proteins can improve the motor function of α-Syn PFF-induced PD mouse models (A. Mechanism of transgenic mouse construction, B. Antifreeze protein CYN-1 improves the motor function of α-Syn PFF-injected mice, C. Antifreeze protein CYN-4 improves the motor function of α-Syn PFF-injected mice).

[0039] Figure 3 Antarctic fish CYN-1 protein reduced the level of α-Syn hyperphosphorylation and aggregation in different brain regions of mice (A: brain slices were immunostained with p_Syn 3 months after unilateral injection of PFF into the striatum; B: mouse brain slices were immunofluorescently stained 3 months after unilateral injection of PFF into the striatum, and the p_Syn intensity in each brain region was quantified (N=3-4 mice per group)).

[0040] Figure 4 Antarctic fish CYN-4 protein reduced the level of α-Syn hyperphosphorylation and aggregation in different brain regions of mice (A: brain slices were immunostained with p_Syn 3 months after unilateral injection of PFF into the striatum; B: mouse brain slices were immunofluorescently stained 3 months after unilateral injection of PFF into the striatum, and the p_Syn intensity in each brain region was quantified (N=3-4 mice per group)).

[0041] Figure 5 Antarctic fish CYN protein reduces α-Syn PFF-induced TH cell damage (α-Syn PFF injection in WT, CYN-1 and CYN-4 mice 3 months after SN-DA neurons were immunofluorescencely stained; B TH-positive neuron cell count). Detailed Implementation

[0042] The Parkinson's syndrome involved in this invention includes "resting tremor," which is often the first symptom, mostly starting in the distal part of one upper limb, and appearing or becoming more pronounced at rest. During an attack, a "pill-rolling" motion is made between the thumb and the flexed index finger.

[0043] The term "muscle rigidity" refers to a condition where the patient's limbs resemble a bent lead pipe, known as "lead pipe rigidity." In patients with resting tremor, intermittent, paused tremors may occur, resembling the turning of a gear, and are termed "cogwheel rigidity." In severe cases, patients may adopt unusual flexed postures or positions, and may even become unable to care for themselves.

[0044] The term "bradykinesia" refers to the early observation that the patient's fine motor skills, such as unbuttoning or buttoning clothes, tying shoelaces, etc., are slow, which is particularly noticeable.

[0045] The "postural balance disorder" mentioned refers to a condition that appears in the middle and late stages of the disease, manifesting as difficulty in standing up and a tendency to fall backward. Sometimes, after taking a step, the patient will walk faster and faster with very small steps and cannot stop in time; this is called a rushing gait or a hurried gait.

[0046] The term "sensory disturbance" refers to the fact that patients may experience a decreased sense of smell in the early stages of the disease, and numbness and pain in the limbs in the middle and late stages of the disease.

[0047] The term "sleep disorder" refers to a patient's vivid dreams at night, accompanied by shouting and limb movements.

[0048] The term "autonomic dysfunction" refers to conditions that patients may experience, such as constipation, excessive sweating, urinary disorders, and orthostatic hypotension.

[0049] The term "mental disorder" refers to the fact that approximately 50% of patients also experience depression, and anxiety is also frequently present. In the later stages of the disease, patients develop cognitive impairment, even dementia, and experience visual hallucinations.

[0050] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to specific embodiments, but it should not be construed as the scope of the present invention being limited to the following embodiments.

[0051] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods, and the experimental materials used in the following embodiments are all available through conventional commercial channels.

[0052] Example 1: Expression and pathological detection of Antarctic fish CYN protein in A53T cells

[0053] A53T is a point mutation of α-synuclein, which is closely related to the pathogenesis and related functional impairments of Parkinson's disease. The A53T cell line is a stably inherited cell line created through transgenic technology, which overexpresses human α-synuclein with a Parkinson's disease-associated mutation (A53T).

[0054] A53T cell lines were cultured in DMEM medium, and Antarctic CYN protein expression plasmids were transfected into A53T cells using Lipo3000 transfection reagent (Invitrogen). Twelve hours after transfection, 5 μg / mL of in vitro synthesized α-Syn PFFs were added to the cells, and the treatment lasted for 48 hours. The level of α-syn phosphorylation (AB_2564891, Abcam) was detected and quantitatively analyzed using immunofluorescence assay.

[0055] First, the cells were washed three times with PBS, then fixed with 4% PFA for 15 minutes, and washed twice with PBS. Next, they were perforated with 0.5% Triton for 15 minutes and blocked with 2% BSA for 1 hour. α-syn phosphorylation antibody (AB_2564891, Abcam) was added and incubated at room temperature for 1 hour, followed by washing three times with PBS. Then, the cells were incubated with secondary antibody (Alexa Fluor 594, Invitrogen) for 1 hour and Hedgehog staining for 5 minutes. Finally, the cells were washed three times with PBS, mounted, and photographed. Fluorescence images were captured using a confocal scanning microscope (LSM710, Carl Zeiss). All images were processed using Zeiss Zen software (Carl Zeiss), and the fluorescence intensity level was assessed using ImageJ.

[0056] The results are as follows Figure 1 As shown, Antarctic fish CYN proteins are derived from tandem repeats of varying numbers of AFPIII domains (see...). Figure 1A) Antarctic CYN protein expression plasmid was transfected into A53T cells using chemical transfection reagents, and the cells were treated with PFF for 48 h. The phosphorylation level and aggregation of α-Syn were then detected. The results showed that Antarctic CYN expression significantly reduced the phosphorylation level and aggregation of α-Syn. Figure 1 (BC) indicates that CYN protein can reduce the phosphorylation level of α-Syn and inhibit the aggregation of α-Syn in vitro.

[0057] Example 2: Establishment of Antarctic fish CYN gene-transfected mice, analysis of their motor abilities, and pathological examination.

[0058] To obtain mice expressing Antarctic fish CYN protein, the CYN gene was inserted into the H11 site of WT (C57BL6) mice via microinjection. These mice were bred according to standard feeding protocols. At 12 weeks of age, in vitro expressed α-syn PFF was injected into the dorsal striatum of WT (C57BL6) and transgenic CYN heterozygous mice via stereotactic brain-targeted injection (AP+0.8mm, ML+2.0mm, DV-4.5mm). Following a single unilateral striatal inoculation with α-syn PFF, WT and transgenic mice (N=7 and N=10 mice, respectively) underwent motor assessments at 3 months (3 mpi), including rotarod fatigue and suspension tests. Results were plotted and analyzed using GraphPad Prism 9.

[0059] Results: To further verify the role of Antarctic fish CYN in Parkinson's disease in vivo, transgenic mice with the Antarctic fish CYN gene inserted at the H11 site were constructed (see...). Figure 2 A). Three-month-old transgenic heterozygous mice were injected with exogenously expressed PFF via striatal brain localization and fed continuously for 3 months. Their motor abilities were then assessed, including rotarod fatigue and suspension tests. Results showed that, compared to WT mice, mice expressing Antarctic fish CYN-1 and CYN-4 proteins exhibited significantly stronger fatigue tolerance and suspension ability. Figure 2 (BC). This indicates that Antarctic fish CYN protein has a protective function in PD model mice.

[0060] Example 3: Establishment of Antarctic fish CYN gene-transformed mice, analysis of their motor abilities, and detection of pathological transformation.

[0061] To confirm the pathological transformation, hyperphosphorylated α-syn(pSyn) deposition, a marker of Lewy bodies, was detected after a single 3 mpi inoculation with PFF. Specifically, the whole brain of mice was fixed with 4% PFA for 24 h after perfusion, followed by dehydration with 30% sucrose solution. Immunofluorescence (IF) was performed on 30 μm thick serial frozen brain sections. Primary antibodies and working dilutions: p-α-syn Ser129 (AB_2564891, Abcam) 1:500; Th (ab_10077691, Abcam) 1:1000. For immunofluorescence studies, sections labeled with the primary antibody were incubated with secondary antibodies (Invitrogen) conjugated to Alexa-fluor 488 or 594. Fluorescence images were acquired using a confocal scanning microscope (LSM710, Carl Zeiss). All images were processed using Zeiss Zen software. ImageJ was used to assess the total number of TH neurons and the level of hyperphosphorylated α-Syn (pSyn) deposition.

[0062] Results: Antarctic fish CYN protein reduced α-Syn phosphorylation levels and aggregation in different brain regions of mice. Three months after unilateral PFF inoculation of the striatum, pathological examination was performed. Immunofluorescence detection of α-Syn phosphorylation levels revealed pathological changes of α-Syn hyperphosphorylation in different brain regions of the control group WT mice, along with dense Lewy body-like aggregates. Figure 3 A). However, CYN-1 mice exhibit milder α-Syn hyperphosphorylation pathology and fewer Lewy body-like aggregates (A). Figure 3 In contrast, CYN-4 mice showed milder α-Syn hyperphosphorylation pathology (AB). Figure 4 (AB). The above results indicate that Antarctic fish CYN protein reduces α-Syn phosphorylation levels and aggregation in different brain regions of mice, thereby alleviating the pathological symptoms of PD.

[0063] Results: Antarctic fish CYN protein reduced α-Syn PFF-induced TH cell damage. Striatal PFF inoculation led to α-Syn pathology in dopamine (SN_DA) neurons of the substantia nigra. In WT mice, α-Syn pathology in the substantia nigra was accompanied by the loss of TH-positive neurons. Figure 5 A) indicates that the generation of intraneuronal α-Syn aggregates leads to the loss of DA neurons, as previously reported. Conversely, α-Syn pathology and the loss of TH-positive neurons were significantly alleviated in CYN-1 and CYN-4 mice. Furthermore, CYN-4 mice showed stronger protective effects against SN_DA neurons compared to CYN-1 mice. Figure 5 B).

[0064] The above results indicate that Antarctic fish CYN protein has a protective effect against the loss of TH-positive neurons induced by striatal PFF inoculation.

Claims

1.A pharmaceutical composition for treating Parkinson's syndrome, the pharmaceutical composition comprising an Antarctic fish protein selected from one or more of CYN-1, CYN-2, CYN-3 and CYN-4 proteins, the nucleotide sequences of the CYN-1, CYN-2, CYN-3 and CYN-4 proteins being shown in SEQ ID NO: 1 to SEQ ID NO: 4, respectively, and the amino acid sequences of the CYN-1, CYN-2, CYN-3 and CYN-4 proteins being shown in SEQ ID NO: 5 to SEQ ID NO: 8, respectively. 2.The pharmaceutical composition of claim 1, wherein the Antarctic fish protein is the CYN-4 protein. 3.The pharmaceutical composition of claim 1, further comprising an additional active ingredient, the additional active ingredient being a drug different from the Antarctic fish protein and capable of improving and / or treating symptoms of Parkinson's syndrome. 4.A use of an Antarctic fish protein in the preparation of a drug for treating Parkinson's syndrome, the Antarctic fish protein being selected from one or more of CYN-1, CYN-2, CYN-3 and CYN-4 proteins, the nucleotide sequences of the CYN-1, CYN-2, CYN-3 and CYN-4 proteins being shown in SEQ ID NO: 1 to SEQ ID NO: 4, respectively, and the amino acid sequences of the CYN-1, CYN-2, CYN-3 and CYN-4 proteins being shown in SEQ ID NO: 5 to SEQ ID NO: 8, respectively. 5.The use of claim 4, wherein the Antarctic fish protein is the CYN-4 protein.

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