485 results about "Synuclein" patented technology

The invention provides application of scEMC10 in treatment and diagnosis of cerebral vascular endothelial cell senescence, and relates to the technical field of biomedicine. The research of the inventor finds that brain microvascular endothelial cell senescence is caused by the lack of scEMC10; after the brain microvascular endothelial cells are treated by scEMC10, beta-galactosidase, SASP and classic senescence markers related to senescence can be down-regulated; after scEmc10 is supplemented to old mice and Alzheimer's disease 5XFAD model mice, the motion coordination ability and the spatial cognitive ability of the mice can be obviously improved, the relative content of a marker phosphorylated alpha-synuclein of the Parkinson's disease of the old mice can be obviously reduced, and the content of tyrosine hydroxylase phosphorylated active forms can be increased. Therefore, the scEMC10 can be used for treating brain microvascular endothelial cell senescence, improving Alzheimer's disease and Parkinson's disease and detecting brain microvascular endothelial cell senescence as a marker.

The invention provides a humanized monoclonal antibody for detecting a human-synuclein oligomer and application of the humanized monoclonal antibody, and belongs to the technical field of biological engineering. The light chain CDR sequence of the binding part comprises at least one of LCDR1, LCDR2 and LCDR3, and the amino acid sequence of the LCDR1 is as shown in SEQ ID NO: 1; the amino acid sequence of the LCDR2 is as shown in SEQ ID NO: 2, and the amino acid sequence of the LCDR3 is as shown in SEQ ID NO: 3. The monoclonal antibody is used as a raw material, and a unique repeated epitope double-antibody sandwich immunodetection method is adopted, so that the human a-Syn oligomer prepared in vitro or in a sample can be detected with high specificity, high sensitivity and high accuracy.

The invention relates to the technical field of environmental health risk evaluation, in particular to a method for evaluating the risk of Parkinson's disease induced by environmental pollutants. The method for evaluating the risk of inducing the Parkinson's disease by the environmental pollutants comprises the following steps: carrying out a subacute exposure experiment by taking caenorhabditis elegans as a model organism; observing the transport capacity of the caenorhabditis elegans, observing and counting the abnormal movement ability of the caenorhabditis elegans, and determining the lipofuscin level of the caenorhabditis elegans, the damage degree of dopaminergic neurons, the dopamine level and the expression and aggregation conditions of alpha-synuclein protein, so as to evaluate the risk of the Parkinson's disease induced by environmental pollutants; the environmental pollutant is 6: 2 chlorinated polyfluoroalkyl ether sulfonate. According to the method, the PD toxicity evaluation model is generated by constructing a behavior characteristic and molecular characteristic scheme and combining multi-strain nematode data, and the problem that in the prior art, the risk of inducing PD by environmental pollutants is difficult to comprehensively reveal due to the fact that a single dimension is concerned is solved.

The invention discloses an early diagnosis and early screening kit for joint detection of Parkinson's disease and application of the kit, and relates to the technical field of medical treatment. The kit is used for combined detection of three proteins, namely alpha synuclein (alpha-Syn), tyrosine 3-monooxygenase / tryptophan 5-monooxygenase activated protein zeta (YWHAZ) and myosin light chain 6 (Myl6), immunochromatography, chemiluminescence and other methods and a double-antibody sandwich method are adopted, the diagnosis efficiency of the YWHAZ protein is prominent, the AUC reaches 0.96, and the detection sensitivity is high. The AUC of Myl6 is 0.92, the AUC of alpha-Syn is 0.82, the joint detection AUC is up to 0.98, the kit is newly added with a time-resolved fluorescence immunochromatography technology, low-background and high-sensitivity detection is realized through a lanthanide-labeled antibody, the change of related protein expression level can be detected in the early stage of Parkinson's disease, early screening and diagnosis are realized, and the kit has the advantages of high specificity, joint detection up to 95%, high sensitivity, high sensitivity and the like. The joint detection reaches 96%, the operation is simple and convenient, and the sample requirement is low.

The present application relates to single-stranded or double-stranded interfering RNA molecules (e.g., siRNAs) that target the alpha synuclein (SNCA) gene. The interfering RNA molecule may contain a specific pattern of nucleoside modification and inter-nucleoside linkage modification as a pharmaceutical composition comprising the interfering RNA molecule. The siRNA molecule may be a branched siRNA molecule, such as a two-branched, three-branched or four-branched siRNA molecule. The disclosed siRNA molecules may also be characterized by a 5 '-phosphorus stabilizing moiety and / or a hydrophobic moiety. In addition, the present disclosure provides methods for delivering siRNA molecules of the present disclosure to a subject, such as the central nervous system of a subject identified as having synucleinopathies.

Provided herein are SNCA antisense oligonucleotides that are capable of modulating the expression of a SNCA target nucleic acid. Also provided herein are methods of use thereof.

The invention relates to the technical field of protein purification, in particular to a purification method of label-free alpha-synuclein. The purification method provided by the invention comprises the following steps: (1) constructing a recombinant expression vector containing an alpha-synaptic nucleus gene; (2) transforming the recombinant expression vector containing the alpha-synucleus gene into host bacteria, carrying out induced expression, centrifuging, and collecting thalli; (3) sequentially carrying out ultrasonic pulverization, boiling and centrifugation on the thalli, and collecting centrifuged supernate; (4) sequentially carrying out ammonium sulfate precipitation, centrifugation, filtration, acid precipitation and alkali neutralization on the supernate to obtain a protein solution to be purified; and (5) carrying out anion exchange chromatography, ultrafiltration and concentration on the to-be-purified protein solution to obtain the label-free alpha-synuclein. The purification method is more efficient, economical and capable of maintaining protein functions, and the method can improve the overall effect and experimental accuracy of alpha-synuclein monomer preparation.

The invention belongs to the technical field of biological detection, and relates to an antibody composition aiming at human pS129-alpha-Syn protein detection and application thereof, and the antibody composition comprises a targeted pS129-alpha-Syn protein phosphorylation antibody and a targeted human alpha-synuclein N-terminal antibody. Meanwhile, based on the antibody composition for detecting the human pS129-alpha-Syn protein, the invention further provides a kit for early diagnosis of the Parkinson's disease. The invention provides an antibody composition aiming at human pS129-alpha-Syn protein detection and application of the antibody composition. The antibody composition is higher in detection specificity and sensitivity.

The present specification provides a monoclonal antibody that specifically binds aggregated, non-phosphorylated α-synuclein and a hybridoma producing it. Also disclosed are methods of generating antibodies that specifically binds aggregated, non-phosphorylated α-synuclein and uses thereof. Uses of anti-α-synuclein antibody in detection and diagnostic assays, and for prophylaxis or therapy of α-synuclein-associated neurodegenerative diseases, are also disclosed.

The invention relates to the technical field of protein purification, in particular to a purification method of label-free A53T mutant alpha-synuclein. The purification method disclosed by the invention is a purification method which is more efficient and economical and can maintain protein functions, 20mg of protein can be obtained by inducing 1L of bacterial liquid for 4 hours through IPTG, and the method can improve the overall effect and experimental accuracy of preparation of the label-free A53T alpha mutant-synuclein monomer.

The present invention relates to an improved antibody specifically binding to amyloid-β oligomers (AβOs). Specifically, the present invention relates to an improved form of the antibody W20. Compared with the antibody W20, the improved form of the antibody W20 has a significantly improved affinity to AβOs, and can more significantly inhibit the aggregation of Aβ and the AβOs-induced toxicity of nerve cells, more effectively improve the cognition and memory functions of an Alzheimer's disease model mouse, and reduce pathological changes in the brain of the mouse. The improved form of the antibody can specifically bind to oligomers of an amyloid-β, α-synuclein, mHTT and SOD 1, can inhibit the aggregation and cytotoxicity of various amyloids, and has a better potential for treating various amyloid diseases, such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, than the antibody W20. The improved form of the antibody can specifically bind to a highly toxic amyloid protein oligomer Aβo*3F, and has a better AD diagnosis value. The amino acid sequence of the antibody W20 is as shown in SEQ ID NO: 1.

The invention discloses a diagnostic marker for Parkinson's disease, application of the diagnostic marker and a heteropolymer detection method, and relates to the technical field of biology. The diagnostic marker is a protein heterozygous aggregate in a brain-derived exosome, and the protein heterozygous aggregate comprises alpha-synuclein and amylin. The invention also provides application of a reagent for detecting the diagnostic marker in preparation of a diagnostic product for Parkinson's disease. According to the present invention, the research results show that the important biomarker protein aggregate in the Parkinson's disease diagnosis is not the aggregate simply formed by polymerizing the alpha-Synuclein (aS) protein, but is doped with the other easily aggregated protein-amylin (Amylin); a heteropolymer composed of aS and Amylin is adopted as a biomarker, and the diagnosis efficiency on the Parkinson's disease can be effectively improved.

The present invention provides improved and minimally invasive biomarker-based diagnostics for synucleinopathies (e.g., Parkinson's disease (PD)). The invention further provides assays and methods for analysis of biological samples, for the evaluation and determination of characteristics pertaining to pathological processes associated with α-synuclein, and to methods for determining the suitability of analytical agents for diagnosis of synucleinopathies. More specifically, the invention in embodiments thereof provides improved methods comprising specific detection and quantification of α-synuclein-based biomarkers from low volumes of biological samples.

The present application relates to novel compounds of formula (I), or a detectably labelled compound, stereoisomer, racemic mixture, pharmaceutically acceptable salt, hydrate, or solvate thereof, that can be employed in the imaging of alpha-synuclein aggregates and determining an amount thereof. Furthermore, the compounds can be used for diagnosing a disease, disorder or abnormality associated with an alpha-synuclein aggregates (such as Parkinson's disease or such as multiple system atrophy (MSA)), determining a predisposition to such a disease, disorder or abnormality, prognosing such a disease, disorder or abnormality, monitoring the evolution of the disease in a patient suffering from such a disease, disorder or abnormality, monitoring the progression of such a disease, disorder or abnormality and predicting responsiveness of a patient suffering from such a disease, disorder or abnormality to a treatment thereof.

To provide novel monoclonal anti-α-synuclein antibodies.SOLUTION: Disclosed is an antibody that can bind to the toxic α-synuclein fragment 1 to 119 / 122 and neutralize this truncated form of α-synuclein. The antibody can be used to treat synucleinopathies such as Parkinson's disease (including idiopathic and hereditary Parkinson's disease), diffuse Lewy body disease (DLBD), Lewy body variant Alzheimer's disease (LBV), combined Alzheimer's and Parkinson's disease, pure autonomic failure, and multiple system atrophy.SELECTED DRAWING: None

The invention belongs to the technical field of biology, and particularly relates to a Parkinson's disease diagnosis kit based on a peripheral red blood cell alpha-synuclein RT-QuIC technology and application of the Parkinson's disease diagnosis kit. The Parkinson's disease diagnostic kit based on the peripheral red blood cell alpha-synuclein RT-QuIC technology comprises a substrate protein, a reaction reagent, a negative reference substance and a positive reference substance, and a sample is selected from red blood cells in blood. The RT-QuIC technology is applied to diagnosis of neurodegenerative diseases, particularly, the sowing activity of pathological alpha-Syn protein is detected in blood red blood cell samples of PD patients of Chinese population for the first time, and the kit has extremely high sensitivity and specificity and provides important reference value for diagnosis and screening of PD. The invention provides a rapid, efficient and accurate diagnostic kit for diagnosis of Parkinson's disease, the kit can be used for accurately detecting Parkinson's disease patients and healthy control, and powerful technical support is provided for clinical diagnosis of the Parkinson's disease patients.

The invention relates to the technical field of biology, in particular to an Alzheimer disease auxiliary detection kit based on a cerebrospinal fluid sample alpha-synuclein seed amplification technology and application of the Alzheimer disease auxiliary detection kit. The Alzheimer disease auxiliary detection kit based on the cerebrospinal fluid sample alpha-synuclein seed amplification technology comprises a substrate protein, a reaction reagent, a negative reference substance and a positive reference substance, and the sample is a to-be-detected cerebrospinal fluid sample. Cerebrospinal fluid of a subject is used as a detection sample for the first time, and clinical diagnosis research on the Alzheimer's disease by the RT-QuIC technology is carried out. The kit has obvious advantages in the aspects of high sensitivity, specificity, repeatability, practicability, rapidness, low cost and the like, the kit is simple in clinical sampling, the detection kit has the characteristics of simple operation process, low cost and the like, the detection time is short, the accuracy and the specificity are high, clinical popularization is easy, and the application prospect is wide. The kit can be clinically used for helping clinicians to diagnose the Alzheimer's disease in an auxiliary manner.

The invention belongs to the field of biological medicine, and particularly relates to application of phosphorylated Parkin protein in preparation of a medicine for treating neurodegenerative diseases carrying pathological alpha-synuclein aggregate characteristics. According to the application, research finds that the Parkin protein and the PINK1 protein have obviously different expression modes in a monkey brain in a physiological state, but the phosphorylation level of the Parkin depends on the expression of the PINK1 protein. Subsequently, it is further found that Parkin phosphorylation expression reduction and obvious aggregation of toxic pS129-alpha-syn occur in both the normal senescent monkey brain and the brain of a sporadic PD patient, and further, it is found through overexpression of wild Parkin that the S65 site phosphorylated Parkin can reduce accumulation of pS129-alpha-syn in the monkey brain, so that the accumulation of pS129-alpha-syn in the monkey brain can be reduced, and the accumulation of pS129-alpha-syn in the monkey brain can be reduced. And the mutant Parkin, which cannot be phosphorylated by PINK1, cannot reduce the aggregation of toxic pS129-alpha-syn. Therefore, the phosphorylated Parkin protein provided by the invention can be used for preparing medicines for treating neurodegenerative diseases carrying pathological alpha-synuclein aggregate characteristics.

The invention discloses a construction method and application of an animal model of Parkinson's disease, and relates to the technical field of animal models of neurodegenerative diseases. The animal model of the Parkinson's disease induces alpha-synuclein to be transmitted along an intestine-brain axis. The construction method comprises the following steps: (1) providing an SD (Sprague Dawley) rat; and (2) performing intragastric administration on the SD rat with rotenone according to the dosage of 30mg / kg / day, so as to obtain the animal model of the Parkinson's disease. The Parkinson's disease modeling method successfully simulates sequential transmission of alpha-syn along the intestine-brain axis, has the advantages of strong targeting, low death rate, endogenous pathology generation and the like, and provides a reliable platform for PD mechanism research and treatment development. According to the screening method of the medicine for treating the Parkinson's disease, the blocking effect of the medicine on PD pathology source transmission can be accurately evaluated by detecting the deposition amount of alpha-syn at multiple parts, and the defects of a traditional model are overcome; the method is suitable for research and development requirements of various drugs, and the application range is far better than that of a screening model only aiming at a single pathological link.

The invention relates to the field of medical diagnosis, in particular to seven interactive genes, a prediction system for predicting transformation of primary fast-moving eye sleep disorder (iRBD) to synucleinopathies and application of the seven interactive genes to preparation of a kit for predicting transformation of the iRBD to the synucleinopathies. According to the prediction system, the median of the model value is innovatively adopted as a critical point to distinguish the transformation risk, so that the prediction accuracy and reliability are remarkably improved. Compared with an existing prediction method, the method shows higher specificity and sensitivity, so that the system can accurately identify high-risk patient groups in the early stage of the disease course. The method has convenience and high efficiency in clinical application. By applying the prediction system to preparation of the kit, the clinical detection process is simplified, so that a doctor can quickly perform detection and obtain a result, and more effective management and treatment on an iRBD patient are realized.

Provided herein is a method comprising: binding α-synuclein to a biolayer interferometry (BLI) microprobe, contacting the BLI microprobe with a biological sample, contacting the BLI microprobe with α-synuclein, and measuring an optical signal from the BLI microprobe, wherein the optical signal indicates whether α-synuclein aggregates have formed on the microprobe.

The invention relates to application of 1-allyl piperazine or pharmaceutically acceptable salt thereof in preparation of a medicine for treating Parkinson's disease. A caenorhabditis elegans PD model is adopted to prove for the first time that on one hand, 1-allyl piperazine can obviously enhance autophagy activity in a model animal body, efficiently promote removal of aggregation alpha-synuclein and radically relieve damage of Parkinson's disease characteristic pathological protein deposition to neurons, and on the other hand, 1-allyl piperazine can effectively promote removal of aggregation alpha-synuclein and radically relieve damage of Parkinson's disease characteristic pathological protein deposition to neurons. The compound can effectively activate mitochondrial unfolded protein reaction. The autophagy activation pathway and the mitochondrial function regulation pathway can generate a synergistic effect to jointly relieve the neurodegeneration process related to the Parkinson's disease, so that dopaminergic neurons are protected, and the pathological progress of the disease is delayed.

The present invention relates to a cell-penetrating peptide and its derivatives to inhibit α-synuclein fibrillation. The present invention specifically relates to a peptide-based inhibitor of Parkinson's Disease. The present invention discloses the identification of the peptides permeable to blood brain barrier for inhibition. α-synuclein fibril formation is observed in the presence of peptides as indicated by SEQ. ID-7, SEQ. ID-8 wherein the SEQ. ID-7, SEQ. ID-8 are truncated versions of SEQ. ID-4 having the homology of 83% and 75% respectively. It provides a peptide having an amino acid sequence of Formula 1. The present invention also provides a pharmaceutical composition comprising a peptide of Formula 1 along with the pharmaceutically acceptable excipient(s) having inhibitory activity against β-sheet polymerisation of amyloidogenic proteins. The analysis showed that peptides corresponding to SEQ. ID-7, SEQ. ID-8 are better inhibitors than SEQ. ID-4 against α-synuclein fibrillation.

The present invention relates to anti-alpha-synuclein antibodies, and uses thereof for treating diseases such as Parkinson's disease.

This invention discloses a method for preparing HVC NPs for the diagnosis and treatment of Parkinson's disease and their applications. The probe HV in the HVC NPs responds to H2O2 and viscosity, utilizing near-infrared fluorescence imaging capabilities to achieve real-time monitoring of Parkinson's disease biomarkers, helping us better understand the occurrence and development of Parkinson's disease. With the assistance of RVG29, the HVC NPs effectively cross the blood-brain barrier. The curcumin within them can reduce cell apoptosis, lower oxidative stress levels, scavenge excess reactive oxygen species, combat inflammation, and reduce α-synuclein aggregation, demonstrating effective anti-Parkinson's disease effects at the cellular and experimental animal levels. This nanomaterial provides a new strategy for integrated research on the diagnosis and treatment of Parkinson's disease.

The invention provides an electrochemical biosensor used for alpha-synuclein detection. The sensor comprises a magnetic particle capture probe coated by a monoclonal antibody, a SiO2 nanoparticle signal probe for detecting antibody modification and a nano porous membrane loaded glassy carbon electrode modified by graphene. During detection, alpha-synuclein is specifically combined with the monoclonal antibody-coated magnetic particle capture probe and the detection antibody-modified cadmium-doped SiO2 nanoparticle signal probe to form a compound with a sandwich structure, the compound is directly precipitated in an external magnetic field, uncombined substances are removed through cleaning, and the detection sensitivity is high. And then re-dispersing the precipitate (compound) in the electrolyte, and immersing the glassy carbon electrode loaded by the graphene-modified nano porous membrane. After electrification, the cadmium ions in the compound are subjected to redox reaction to generate a current signal, and the current intensity of the current signal is in direct proportion to the content of alpha-synuclein. The sensor has the advantages of simplicity in operation, rapidness in detection, high sensitivity, high specificity and the like.

A method for the prevention and / or treatment of depression and / or anxiety related to Parkinsonism, such as an alpha-synucleinopathy, includes administering to a subject a composition including a therapeutically effective amount of at least one compound of formula (I) and / or of formula (Ia).

This disclosure provides recombinant DNA mol-encoding fusion proteins that are able to regulate expression of alpha-synuclein. Also provided are various compositions comprising the recombinant DNA molecules, as well as associated methods of use. The recombinant DNA molecules and associated methods are useful for the treatment of subjects having disorders caused by excess expression or intracellular accumulation of alpha-synuclein, including Parkinson's disease.

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 invention discloses a construction method and application of a Lewy small body dementia animal model, and belongs to the technical field of animal model construction. The construction method comprises the following steps: obtaining a phosphatase and tensin homologous gene-induced kinase 1 gene knockout experimental animal A by using a gene editing technology, and carrying out hybrid breeding on the experimental animal A and an Alzheimer disease model experimental animal B simulating beta-amyloid protein (Abeta) pathology, and screening filial generations containing the Alzheimer disease related mutation and pink1 gene knockout at the same time. According to the constructed model, beta amyloid protein is deposited on the basis of pink1 gene knockout, beta-amyloid plaque (A beta) is used for inducing alpha-synuclein protein aggregation, Lewy bodies are widely generated in cortex and hippocampus, the occurrence and development process of DLB is simulated, and a reliable animal model is provided for disease mechanism research and treatment drug screening and development.