41 results about "Synuclein" patented technology

The present invention relates to novel molecules that can be employed for the prevention, alleviation, treatment and / or diagnosis of diseases, disorders and abnormalities associated with alpha-synuclein (α-synuclein, A-synuclein, aSynuclein, A-syn, α-syn, aSyn, a-syn) aggregates, including, but not limited to, Lewy bodies and / or Lewy neurites, such as Parkinson's disease, Multiple System Atrophy, Lewy Body dementia (LBD; dementia with Lewy bodies (DLB) (“pure” Lewy body dementia), Parkinson's disease dementia (PDD)) or Diffuse Lewy Body Disease. The invention relates to alpha-synuclein binding molecules, in particular to alpha-synuclein antibodies or an antigen-binding fragment or a derivative thereof and uses thereof. The present molecules can also be used for determining a predisposition to such a disorder, disease or abnormality, monitoring residual disorder, disease or abnormality, or predicting the responsiveness of a patient who is suffering from such a disorder, disease or abnormality to treatment with a certain medicament.

The disclosure provides peptide compositions and immunotherapy compositions comprising an amyloid-beta (Aβ, Abeta) peptide, a tau peptide, and an alpha-synuclein peptide. The disclosure also provides methods of treating or effecting prophylaxis of Alzheimer's disease or other diseases with beta-amyloid deposition in a subject, including methods of clearing deposits, inhibiting or reducing aggregation of Aβ and tau and an alpha-synuclein, blocking the uptake by neurons, clearing amyloid, and inhibiting propagation of tau seeds and an alpha-synuclein synucleinopathies in a subject having or at risk of developing Alzheimer's disease or other diseases containing tau and amyloid-beta and an alpha-synuclein accumulations. The methods include administering to such patients the compositions comprising an amyloid-beta (Aβ) peptide and a tau peptide and an alpha-synuclein peptide.

The present invention provides novel irisin peptides (e.g, irisin glycosylation mutants and biologically active fragments thereof). Also provided are methods for preventing or reducing degeneration of dopaminergic neurons and / or preventing or ameliorating at least one motor deficit in a subject in need thereof, such as in a subject with α-synucleinopathy, using the novel irisin peptides to modulate irisin-induced integrin signaling. The novel irisin peptides can also be used in methods for increasing expression of brain-derived neurotrophic factor (BDNF), and / or treating or preventing neurological diseases or disorders that would benefit from decreased neuronal cell death and / or increased neuronal survival in a subject. In addition, the novel irisin peptides may be used in methods for preventing or treating muscular atrophy or muscular dystrophy.

The present invention relates to a DNA aptamer specifically binding to an alpha-synuclein protein and uses thereof. Specifically, the present invention relates to a DNA aptamer selected from the group consisting of nucleotide sequences of SEQ ID NOS: 1 to 12 and binding specifically to an α-synuclein protein, and a composition for detecting an α-synuclein protein, a detection kit, a detection chip or a microarray, all comprising the aptamer as an active ingredient. In addition, the present invention relates to a method for detecting an α-synuclein protein, a method for providing information for diagnosing a degenerative brain disease, a composition for diagnosing a degenerative brain disease, and a pharmaceutical composition for preventing or treating a neurodegenerative disease, all using the DNA aptamer of the present invention.

The present application relates to the technical field of biological medicine, in particular to the application of 1-allyl piperazine in the preparation of drugs for preventing and treating Parkinson's disease. The present application discloses for the first time that 1-allyl piperazine can significantly inhibit the aggregation of alpha-synuclein in vitro. 1-allyl piperazine can significantly reduce the cytotoxicity induced by alpha-synuclein aggregation, and 1-allyl piperazine can effectively interfere with the liquid-liquid phase separation process of alpha-synuclein. It is also found through computer simulation data that 1-allyl piperazine can interact with the target (alpha-synuclein). It is proved that the 1-allyl piperazine has an anti-Parkinson's disease effect and can be applied to the preparation of Parkinson's disease prevention and treatment preparations.

This invention relates to a mouse model of Parkinson's disease and its applications. The construction method includes the following steps: 1) in mice... Snack An exogenous fragment containing the human SNCA G51D coding sequence was knocked into the region upstream of the gene stop codon via homologous recombination, causing the human SNCA G51D coding sequence to interact with the mouse endogenous gene. Snack The gene forms a bicistronic expression structure, and the coding sequence of the human SNCA G51D is shown in SEQ ID No:1; 2) Positive F0 generation mice are backcrossed with wild-type mice, and genotypes are identified and screened to obtain a stable SNCA G51D endogenous knock-in Parkinson's disease mouse model. The gene editing strategy of the Parkinson's disease mouse model preserves the mouse's... Snack Simultaneous endogenous expression of α-synuclein G51D in the gene can mimic two pathogenic forms, exhibiting high physiological relevance and genetic authenticity.

The present invention provides small molecule drugs and pharmaceutical compositions for the treatment and prevention of diseases related to the formation of certain types of oligomers in a subject. More specifically, the drugs and compositions reduce or prevent the formation of oligomers formed from tau protein, TDP-43, Huntingtin's protein and / or alpha-synuclein. It further provides a method of reducing formation of or disrupting TDP-43, alpha-synuclein, Huntingtin's protein and / or tau protein oligomers in a subject, the method comprising the step of administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition.

The application discloses an in-vitro detection method and kit for O-GlcNAc glycosylation modification of alpha-synuclein, and relates to the field of biochemical detection. Y289L The method comprises the following steps: extracting protein in a sample to be detected, adding UDP-GalNAz substrate beta4GalT Y289L The mutant enzyme and the reaction are carried out to obtain a protein system; DBCO-mPEG is added to the protein system, and the reaction product is subjected to electrophoretic separation; and according to an electrophoretogram, the proportion of the protein subjected to glycosylation modification and the molecular weight distribution thereof are calculated. The application marks specific molecular weight "tags" for O-GlcNAc glycosylation proteins, and the glycosylation-modified proteins are recognized by alpha-synuclein specific antibodies to show specific molecular weight sizes; and the alpha-synuclein polymerization states, such as dimers and polymers, subjected to O-GlcNAc glycosylation modification can be determined and quantified according to protein standards.

Provided herein are SNCA antisense oligonucleotides (ASOs) and SNCA ASO conjugates for modulating expression of a SNCA target nucleic acid. Also provided herein are methods of use thereof.

The present invention relates to compounds represented by the general formulas Ia, Ib, IIa, or IIb (see Formulas). These compounds are suitable for imaging alpha-synuclein and for diagnosing diseases associated with alpha-synuclein aggregation. The compounds are also useful for the treatment and prevention of diseases associated with alpha-synuclein aggregation.

This disclosure describes compositions and methods for treating Parkinson's Disease by targeting production and secretion of α-synuclein. This disclosure identifies mechanisms by which α-synuclein aggregates form and provide compositions and methods of treatment that inhibit and / or ameliorate the effects of α-synuclein aggregates in Parkinson's Disease.

Disclosed are substituted heterocyclic compounds of formula (I) and pharmaceutically acceptable salts thereof, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha-synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, this invention relates to a method of using the compounds of formula (I) as tracers in positron emission tomography (PET) imaging to study tau deposits in brain in vivo to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. The disclosure further relates to a method of measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.

The present disclosure is based, in part, on the discovery of antibodies, such as BAN0805, that selectively target human alpha-synuclein aggregates, such as oligomers / fibrils. BAN0805 has a lower propensity to bind to undesired monomeric alpha-synuclein targets compared to mouse monoclonal antibody mAb47.

The present disclosure describes a method of reducing Miro1 and / or phosphorylated alpha-synuclein level in a cell, for example, by contacting the cell with an effective amount of a T-type calcium channel antagonist or a ferroptosis inhibitor.

The application is directed to compounds of formulae (IA) and (IB) and their salts and solvates, wherein R1a, R2a, R3a, A1, A2, A3, R1b, R2b, R3b, B1, and B2 are as set forth in the specification, as well as to methods for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and / or prevention of, e.g., lysosomal storage diseases, such as Gaucher's disease, and α-synucleinopathies, such as Parkinson's disease.

This invention discloses the application of bimatoprost in the preparation of drugs for the prevention and / or treatment of Parkinson's disease, within the field of drug reuse. Bimatoprost is a prostaglandin F2α analog, currently mainly used for glaucoma and eyelash growth. This invention has found that bimatoprost can improve Parkinson's disease-related behavioral disorders, increase the expression of tyrosine hydroxylase, a protein associated with dopaminergic neurons in the substantia nigra, and reduce the abnormal accumulation of α-synuclein, thus exhibiting good ameliorative and protective effects against Parkinson's disease. This invention provides a new drug option for the treatment of Parkinson's disease.

A compound of formula I for use in a method for treating or preventing synucleinopathy is provided, comprising administering a therapeutically effective amount of said compound (I): or a pharmaceutically acceptable salt or hydrate thereof, to a subject.

The application discloses genetically engineered ferritin against alpha synuclein, a preparation method and application thereof, and belongs to the technical field of biological medicine and protein engineering. The genetically engineered ferritin is constructed by fusing and expressing NACore polypeptide and human heavy chain ferritin through gene recombination technology, and has alpha synuclein aggregation inhibition activity. The genetically engineered ferritin can specifically combine with the NAC region of alpha synuclein, significantly inhibits the misfolding and aggregation of alpha synuclein, and provides a new drug raw material and treatment strategy for the treatment of Parkinson's disease and other alpha synuclein related neurodegenerative diseases. The genetically engineered ferritin prepared by the application has uniform particle size distribution and stable physicochemical properties. Molecular simulation verifies that the genetically engineered ferritin can efficiently combine with the NAC region of alpha synuclein. ThT fluorescence detection and CCK-8 experiments prove that the genetically engineered ferritin can inhibit the aggregation and fibrosis of alpha synuclein, and lays a solid foundation for the clinical treatment of related diseases.

This application relates to the field of biomedicine, specifically to the use of small molecule compounds in the preparation of drugs for the treatment and / or prevention of α-synuclein diseases, wherein the small molecule compounds are selected from at least one of AO-365 / 43264238 and AG-670 / 40728295. The small molecule compounds provided in this invention can precisely target and interfere with α-syn-VAPB interactions, improving neuronal damage caused by abnormal aggregation of α-synuclein, thereby safely and effectively treating and / or preventing α-synuclein diseases, particularly Parkinson's disease.

The present invention relates to compounds of formula (I) as TMEM175 modulators for reducing alpha-synuclein aggregation for the treatment of Parkinson's disease.

The present invention relates to novel monoclonal anti-alpha-synuclein antibodies. These antibodies can be used to treat synucleinopathies, such as Parkinson's disease (including idiopathic and genetic forms of Parkinson's disease), diffuse Lewy body disease (DLBD), Lewy body variant of Alzheimer's disease (LBV), combined Alzheimer's and Parkinson's disease, pure autonomic failure, and multiple system atrophy.

The present invention is characterized by a multinucleotide construct comprising a sequence targeting α-synuclein mRNA. Constructs comprising the sequence targeting α-synuclein mRNA and / or its coding sequence can be used, for example, to inhibit α-synuclein mRNA expression and / or to treat synucleinosis diseases or conditions.

Abstract The present invention provides novel methods of identifying, monitoring or determining the risk of developing a protein misfolding neurodegenerative disorder in a subject, particularly an alpha synucleinopathy (including Parkinson’s disease and dementia with Lewy bodies) using extracellular vesicle samples. Corresponding methods for selecting a treatment and assaying for the presence of a pathological prion-like protein (or one or more ceramide species) in an extracellular vesicle sample are also provided. Abstract The present invention provides novel methods of identifying, monitoring or determining the risk of developing a protein misfolding neurodegenerative disorder in a subject, particularly an alpha synucleinopathy (including Parkinson's disease and dementia with Lewy bodies) using extracellular vesicle samples. Corresponding methods for selecting a treatment and assaying for the presence of a pathological prion-like protein (or one or more ceramide species) in an extracellular vesicle sample are also provided. 20 24 27 84 87 17 D ec 2 02 4 A b s t r a c t 2 0 2 4 2 7 8 4 8 7 1 7 D e c 2 0 2 4

The application relates to the field of biological medicine, in particular to application of a small molecule compound in preparation of a medicine for treating and / or preventing alpha-synuclein disease, wherein the small molecule compound is at least one selected from AO-365 / 43264238 and AG-670 / 40728295. The small molecule compound provided in the embodiment of the application can precisely target and interfere with alpha-syn-VAPB interaction, improve neuron damage caused by abnormal aggregation of alpha-synuclein, thereby safely and effectively treating and / or preventing alpha-synuclein disease, in particular, Parkinson's disease.

This description refers to antisense oligonucleotides that act on SNCA mRNA (e.g., at an intron-exon junction) in a cell, resulting in reduced expression of the SNCA protein. Reduced SCNA protein expression is beneficial for the treatment of certain medical conditions, such as a neurological disorder.

This document discloses methods for treating protein diseases involving proteins targeted by the chaperone function of nuclear transporter β1 (Kpnβ1). Therefore, the method of this application is for enhancing the chaperone function of Kpnβ1 and includes administering an effective amount of one or more compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, or XVI to an individual in need. This method can be used, for example, to treat protein diseases involving TDP-43, SOD1, or α-synuclein, or fragments and / or isoforms thereof, and / or other proteins targeted by the chaperone function of Kpnβ1, and thus for treating individuals with neurodegenerative diseases. Formula (I)

This invention belongs to the field of physical therapy technology for Parkinson's disease, and provides a non-invasive closed-loop feedback vagus nerve electrical stimulation system for the prevention and treatment of Parkinson's disease. The system includes: a high-frequency electrical stimulator hardware subsystem, transcutaneous nerve stimulation electrodes, a respiratory and heart rate signal acquisition and closed-loop feedback subsystem, and a high-frequency electrical stimulator software subsystem. This invention uses kilohertz stimulation pulses to bidirectionally modulate the vagus nerve, activating afferent C fibers and initiating the anti-inflammatory neural pathway of locus coeruleus noradrenergic neurons, thus alleviating central inflammation. Simultaneously, it blocks A and B efferent fibers, inhibiting mediated α-synuclein retrograde axonal transport. Through multimodal physiological signal monitoring and embedded intelligent algorithms, it achieves real-time, closed-loop, and personalized control of stimulation parameters and automatic switching of stimulation modes, optimizing efficacy and improving safety. Through adhesive electrodes and acquisition devices, it achieves completely non-invasive, wearable, and home-based treatment.

This disclosure provides (i) a benzo[c][1,2,5]thiadiazolyl-based target ligand that can bind to toxic peptides and / or protein aggregates in brain tissue (e.g., α-synuclein fibrils, amyloid plaques, and / or tau tangles) for degradation; (ii) a ubiquitin ligase mobilizing ligand; and (iii) a proteolytically targeted chimera containing a linker between (i) and (ii). These proteolytically targeted chimeras are useful for treating neurodegenerative disorders such as Parkinson's disease (PD), multiple system atrophy (MSA), and Lewy body dementia.

The disclosure relates to formulations of double stranded ribonucleic acid (dsRNAi) agents targeting a SNCA gene, as well as methods of inhibiting expression of a SNCA gene and methods of treating subjects having a SNCA-associated neurodegenerative disease or disorder, e.g., Parkinson's Disease (PD), multiple system atrophy, Lewy body dementia (LBD), among other synucleinopathies, using such dsRNAi agents formulations.

The present application relates to the technical field of biometrics and in vitro diagnosis standardization, and particularly relates to a preparation and value determination method of alpha-synuclein solution standard substance, comprising the following steps: cloning a gene coding alpha-synuclein into a prokaryotic expression vector for recombinant expression, purifying the protein raw material with purity greater than or equal to 99% through affinity chromatography and ion exchange chromatography; diluting and sub-packaging the protein raw material for storage to obtain the solution standard substance; determining the value of the standard substance by using an isotope dilution mass spectrometry method based on amino acid analysis, calculating the mass concentration value by measuring the peak area ratio of stable amino acids and isotope-labeled amino acids after hydrolysis, and tracing the value to the international unit system through the amino acid primary standard substance; and performing uniformity testing and stability investigation on the standard substance, solving the problem of lack of standard substance with metrological traceability in the alpha-synuclein detection field, and obtaining the standard substance which can be used for value transmission and detection result standardization among different in vitro diagnosis platforms.