34 results about "Amyloid Protein Precursor" patented technology

An L-form ribonucleic acid (L-RNA) aptamer-antisense oligonucleotide (ASO) conjugate comprise the L-RNA aptamer, which comprises a ribonucleic acid sequence. The ASO comprises a deoxyribonucleic acid sequence selected from a group. A method of imaging amyloid precursor protein (APP) rG4 in a cell comprising transfecting the cell with a messenger RNA of APP, permeating the cell, contacting the permeated cell with a cyanine3 (Cy3) labeled APP nucleic acid probe and the L-RNA aptamer-ASO conjugate, and subjecting the product to fluorescence microscopy analysis to produce an image of the APP rG4 in the cell.

Described herein are methods for identifying and measuring one or more non-classical variant(s) of amyloid precursor protein (APP) gene. Provided herein are methods for diagnosing and treating an individual having or suspected of having Alzheimer's disease following identification of an expression profile or an activity profile of the one or more non-classical variant(s).

Described herein are methods for inhibiting generation of one or more non-classical variant(s) of amyloid precursor protein (APP) gene. Provided herein are methods for diagnosing an individual having or suspected of having Alzheimer's disease following identification of an expression profile or an activity profile of the one or more non-classical variant(s) and treating the individual using a reverse transcriptase inhibitor or salt thereof.

The present invention provides siRNA, peptide oligonucleotide drugs, and their applications for suppressing the expression of the amyloid precursor protein (APP) gene in human cells. The siRNA exhibits potent activity in inhibiting APP expression. Through appropriate modifications, its ability to silence the target is enhanced while reducing off-target activity. The described siRNA and its conjugates hold promise for clinical application in the prevention and treatment of diseases associated with the APP target, including cerebral amyloid angiopathy (CAA), early-onset familial Alzheimer's disease (EOFAD), or Alzheimer's disease (AD).

There are disclosed therapies and preventions of prion protein complex infections. The transcription of the amyloid precursor protein gene and PrP gene and the RNA transcript are the rate-limiting steps and are most susceptible for blockage and control of the process of amyloid protein formation and PrPsc formation. Thus, therapies and prevention regimes for prion protein complex infections interrupt this process at the level of DNA transcription to RNA, RNA transport to the mitochondrion for protein synthesis and deposition in the cerebral cortex neurons.

In one aspect, methods of diagnosing a subject as having Alzheimer's disease and prognosing a subject as being at risk of progressing to Alzheimer's disease are provided. In some embodiments, the method comprises determining one or more of the level of expression of rhotekin 2 (RTKN2), the level of expression of microtubule-associated Ser / Thr kinase 4 (MAST4), the level of binding of forkhead box O1 (FOXO1) to the RTKN2 promoter, and the level of binding of amyloid precursor protein (APP) to the MAST4 promoter in a sample from the subject.

Compositions and methods useful to reduce expression of amyloid precursor protein (APP) gene and for treatment of APP-associated diseases and conditions are provided. Provided are APP dsRNA agents, APP antisense polynucleotide agents, compositions comprising APP dsRNA agents, and compositions comprising APP antisense polynucleotide agents that can be used to reduce APP expression in cells and subjects.

This disclosure pertains to the field of biomedicine, specifically relating to double-stranded oligonucleotides targeting the APP gene and their applications. Specifically, it provides double-stranded oligonucleotide agents or their salts, conjugates, or compositions for inhibiting amyloid precursor protein (APP) expression, wherein the double-stranded oligonucleotide agent comprises a sense strand and an antisense strand forming a double-stranded region; wherein the antisense strand sequence comprises at least 15 consecutive nucleotides of any of the sequences shown in SEQ ID NO:1-154 with a difference of no more than 3 nucleotides, and / or the sense strand sequence comprises at least 15 consecutive nucleotides of any of the sequences shown in SEQ ID NO:155-308 with a difference of no more than 3 nucleotides. The double-stranded oligonucleotide agent or its salt for inhibiting APP expression disclosed in this application can significantly inhibit APP expression and can be used for the prevention and / or treatment of diseases or conditions mediated by the APP gene and / or associated with protein amyloidosis.

Disclosed is a double-stranded RNA that has a first strand and a second strand complementary to the first strand. The first strand has: a main sequence which comprises 19-23 nucleotides and in which the nucleotide at the 5'-end is guanine (G) or cytosine (C); and an additional sequence which comprises 2-4 nucleotides and is added to the 3'-end side of the main sequence. The main sequence comprises a portion of a nucleotide sequence encoding an amyloid precursor protein, wherein the portion includes at least a portion of a nucleotide sequence encoding a signal peptide region of the amyloid precursor protein.

The invention relates to siRNA (small interfering Ribonucleic Acid) for inhibiting mRNA (messenger Ribonucleic Acid) expression of amyloid precursor protein APP (Amyloid Protein) as well as a conjugate, a pharmaceutical composition and application of the siRNA. The siRNA comprises a positive-sense strand and an antisense strand, and each nucleotide in the siRNA is independently modified or unmodified nucleotide; the positive-sense strand comprises a nucleotide sequence selected from one of nucleotide sequences as shown in SEQ ID NO.1 to 103 or a nucleotide sequence with no more than 3 base mutations of the nucleotide sequences as shown in SEQ ID NO.1 to 103, and the antisense strand comprises a nucleotide sequence selected from one of nucleotide sequences as shown in SEQ ID NO.106 to 208 or a nucleotide sequence with no more than 5 base mutations of the nucleotide sequences as shown in SEQ ID NO.106 to 208. The siRNA, the conjugate thereof and the pharmaceutical composition disclosed by the invention have good stability and relatively high APP mRNA (messenger Ribonucleic Acid) inhibitory activity.

An RNAi agent targeting an amyloid precursor protein, such as a double-stranded small interfering RNA (siRNA) agent. A method for inhibiting the expression of the APP gene by using the RNAi agent and a method for preventing and treating APP-related diseases, such as cerebral amyloid angiopathy (CAA) or Alzheimer's disease (AD), including early-onset familial Alzheimer's disease (EOFAD). The siRNA significantly inhibits the expression level of the APP gene and has a long-lasting drug effect.

The present invention provides a medicine for treating a neurodegenerative disease, which employs LEFTY2 (Left-Right Determination Factor 2) generated by co-culturing mesenchymal stem cells of mammals with nerve cells having mutations in the APP (Amyloid precursor protein) gene, or a specific protein. The LEFTY2 has an effect of inhibiting Beta amyloid and a hyperphosphorylated neuronal microtubule-associated protein (Tau protein), without affecting the development of nerve cells and having the ability to promote the growth of the nerve cells; and the two types of proteins have a crucial impact on the neurodegenerative diseases.

Described herein are methods for identifying and measuring one or more non-classical variant(s) of amyloid precursor protein (APP) gene. Provided herein are methods for diagnosing and treating an individual having or suspected of having Alzheimer's disease following identification of an expression profile or an activity profile of the one or more non-classical variant(s).

The invention relates to a polypeptide drug for preventing and treating Alzheimer's disease, which can safely and effectively reduce the protein level of PS1 in AD and inhibit amyloid pathway metabolism of amyloid precursor protein so as to improve pathological deposition of beta amyloid protein in AD. Through an endogenous PS1 protein polypeptide fragment, the effect that PS1 is used for inhibiting PS1 is realized, the specificity is high, the safety is good, the curative effect is exact, the molecular weight is small, and under the help of a cell-penetrating peptide Tat sequence, the PS1 protein polypeptide fragment easily penetrates through a blood brain barrier and smoothly reaches an AD susceptible region to play a role; besides, the compound is easy to synthesize and low in preparation cost, has obvious and unique advantages compared with small molecule chemical inhibitors and monoclonal antibody drugs, can become ideal drugs for preventing and treating AD, and has high clinical conversion value.

The present invention relates to the field of lysosome-targeted degradation, and particularly relates to the use of a technology for targeted degradation of intracellular amyloid deposits in the preparation of drugs for neurodegenerative diseases. The present invention provides the use of a nanochimera in the preparation of a drug for treating neurodegenerative diseases, wherein the nanochimera comprises a first protein and an ABIcs protein tag, and the first protein is selected from the group consisting of α-synuclein, tau protein, amyloid precursor protein, huntingtin protein, and TAR DNA-binding protein 43. The nanochimera provided by the present invention can not only target intracellular amyloid aggregates, but also the amyloid aggregates inserted into the nanochimera can be efficiently degraded through the lysosomal pathway, with high safety.

The present application relates to a peptide having inhibitory activity against amyloid precursor protein and uses thereof, and provides a peptide consisting of any one of the amino acid sequences set forth in SEQ ID NOs: 1 to 8 and SEQ ID NOs: 20 to 23, and a pharmaceutical composition for preventing or treating degenerative neurological diseases comprising the peptide as an active ingredient.

Described herein are CRISPR / Cas9 constructs designed for the C-terminal truncation of human amyloid precursor protein (APP) as well as methods of making and using such a construct.

The invention relates to the field of human genetics, more specifically to treatments for a disease or condition associated with an abnormal processing of the Amyloid Precursor Protein (APP), preferably familiar Alzheimer disease (FAD). The invention in particular relates to antisense oligonucleotides (AON's) that can be used for treating such diseases or conditions.

Inhibitors are provided for targeting γ-secretase to reduce amyloid load as a viable strategy in Alzheimer's disease treatment and drug discovery. γ-secretase has been shown to cleave amyloid precursor protein, causing an increase in the extracellular concentration of amyloid-β peptides. This extracellular concentration increase can lead to a build-up of amyloid plaques in patients and associated health complications for them. The inhibitors bind adjacent the transmembrane domain of amyloid precursor protein through both covalent and non-covalent interactions. These interactions inhibit the ability of γ-secretase to cleave the amyloid precursor protein, halting the build-up of extracellular amyloid plaques. The inhibitors exhibit specificity for amyloid precursor proteins, reducing concerns of potential off-target effects.

The invention relates to the technical field of polypeptide drugs for treating neurodegenerative diseases, in particular to a polypeptide blocking agent for inhibiting transcellular transport of alzheimer's disease astrocyte GFAP (glial fibrillary acidic protein) to neurons and application of the polypeptide blocking agent. According to the technical scheme, the interaction between the GFAP and the APP (amyloid precursor protein) can be used as an AD (Alzheimer's disease) intervention target, then polypeptide drugs are developed, and the blocking peptide targeting the binding interface between the N terminal of the APP and the GFAP is designed. The medicine can remarkably improve cognitive impairment of AD model mice by inhibiting GFAP endocytosis, repairing mitochondrial functions, relieving neuroinflammation and other mechanisms. According to the technical scheme, the technical problem that polypeptide drugs capable of targeting and interfering GFAP related pathological processes are lacked in the prior art can be solved, a brand new strategy is provided for early intervention of AD, and the technical scheme has important clinical transformation value.

The present invention relates to novel amyloid - β (Aβ) - binding molecules, in particular Aβ antibodies or antigen - binding fragments thereof and / or their uses. The provided molecules can also be used to determine the predisposition to amyloid - β - related diseases, disorders or conditions, monitor the residual impairment of a disease or condition, or predict the responsiveness of a patient suffering from such a disease or condition to treatment with a specific drug. Accordingly, the present invention relates to novel molecules useful for diagnosing amyloid - β - related diseases, disorders or conditions. A sandwich immunoassay can be based on capturing and detecting an amyloid - β - binding antibody or an antigen - binding fragment thereof, wherein one or the other of the capturing or detecting antibody or antigen - binding fragment shows no cross - reactivity with soluble amyloid precursor protein (APP). Another amyloid - β - binding antibody or antigen - binding fragment can show cross - reactivity with soluble amyloid precursor protein (APP) without compromising the specificity of the assay for soluble APP.

A gene expression regulator containing microparticles containing miRNA which targets a gene related to the expression of at least one kind of protein of amyloid precursor protein (APP), β-secretase (BACE1), an NMDA-activating protein, glycogen synthase kinase-3β (GSK-3β) and polyglutamine-binding protein-1 (PQBP1) can provide a novel gene expression regulator which can regulate (suppress, inhibit or the like) the expression of a protein related to amyloid β-related or tau protein-related dementia or brain inflammation such as Alzheimer's disease; an agent for preventing or treating Alzheimer's disease; and a method for improving dementia.

There are disclosed therapies and preventions of prion protein complex infections. The transcription of the amyloid precursor protein gene and PrP gene and the RNA transcript are the rate-limiting steps and are most susceptible for blockage and control of the process of amyloid protein formation and PrPsc formation. Thus, therapies and prevention regimes for prion protein complex infections interrupt this process at the level of DNA transcription to RNA, RNA transport to the mitochondrion for protein synthesis and deposition in the cerebral cortex neurons.

The present invention relates to the use of mitoxantrone hydrochloride as a therapeutic drug for the treatment of neurodegenerative disorder in a subject, wherein the mitoxantrone hydrochloride is an inhibitor of β-amyloid precursor protein (APP) and leucine-rich repeat kinase 2 (LRRK2), capable of inhibiting APP and LRRK2 protein levels in the subject.

The invention discloses an application of sildenafil in preparation of a medicine for improving cell ciliary dysfunction. According to the application disclosed by the invention, an airway ciliary dysfunction mouse model prepared by a double transgenic mouse for expressing chimeric mouse / human amyloid protein precursor protein (Mo / HuAPP695swe) and mutant human premature protein 1 (PS1-dE9) is jointly treated by hypoxia and a Flk-1 / KDR inhibitor (Semaxanib), and is subjected to intragastric administration with sildenafil; it is verified that sildenafil can relieve the progress of ciliary dysfunction of two model mice, especially improve the functions of lung tissue, cortex and hippocampus cell movement cilia and primary cilia, and a strategy of an action mechanism is provided for understanding that sildenafil serves as a targeted drug for improving ciliary dysfunction.

Described herein are biological devices and extracts useful for detecting Alzheimer's disease and / or concussions. The biological devices include microbial cells transformed with a DNA construct containing genes for producing β-amyloid precursor protein, microtubule associated protein tau, adipose triglyceride lipase, acyl-CoA dehydrogenase, and O-linked N-acetylglucosamine transferase. In some instances, the biological devices also include a gene for enhanced green fluorescent protein. Methods for using the devices to diagnose or detect Alzheimer's disease and / or concussions are also provided herein.

The invention belongs to the technical field of biological medicine, and relates to a method for preparing PAPA / siRNA nanoparticles by adopting a delivery carrier PAH-AM-PEG-ApoE (159-167) 2 (PAPA) modified by apolipoprotein E (ApoE) peptide through an electrostatic binding self-assembly method by designing and screening a siRNA sequence aiming at beta-site amyloid precursor protein cutting enzyme 1 (BACE1) and glycogen synthase kinase-3beta (GSK3beta) and adopting a delivery carrier PAH-AM-PEG-ApoE (159-167) 2 (PAPA) modified by ApoE peptide. The siRNA nano delivery system constructed by the invention aims to explore a new way for AD treatment.

There are disclosed therapies and preventions of prion protein complex infections. The transcription of the amyloid precursor protein gene and PrP gene and the RNA transcript are the rate-limiting steps and are most susceptible for blockage and control of the process of amyloid protein formation and PrPsc formation. Thus, therapies and prevention regimes for prion protein complex infections interrupt this process at the level of DNA transcription to RNA, RNA transport to the mitochondrion for protein synthesis and deposition in the cerebral cortex neurons.

Methods of treating and preventing prion protein complex infection are disclosed. Transcription of an amyloid protein precursor protein gene and a PrP gene and RNA transcription are speed limiting steps, and the process of amyloid protein formation and PrPsc formation is most easily blocked and controlled. Thus, the regimen for the treatment and prevention of prion protein complex infection interrupts this process at the level of DNA transcription to RNA, RNA transport to mitochondria for protein synthesis and deposition at cerebral cortical neurons.