302 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.

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 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 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 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.

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 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.

Disclosed is a method of treating a neurodegenerative disease such as Parkinson's disease, diffuse Lewy body disease, transitional Lewy body dementia, and multiple system atrophy in a subject. The method comprises administering to the subject a therapeutically effective amount of a peptide comprising an α-synuclein binding domain operably linked to a protein transduction domain and a proteasomal targeting domain, wherein the α-synuclein binding domain is derived from a reversed sequence of β-synuclein. Other methods, as well as uses and compositions, are disclosed.

The present invention relates to methods of treating early multiple system atrophy (MSA) or MSA-C using anti-alpha synuclein antibodies, such as Amlenetug.

The present application relates to the field of medical detection, in particular to a detection reagent, a detection kit and a detection method of amyloid aggregates. The present application provides a seed amplification test method of pathological alpha-synuclein aggregates, which coats or fixes specific anti-alpha-Syn antibodies on the bottom and side of an enzyme-labeled plate, captures pathological alpha-Syn aggregates in the sample, washes off unbound alpha-Syn or other substances, effectively removes various interference amplification factors in the sample, and incubates and amplifies in a buffer containing alpha-Syn monomers in a vibration-intermittent vibration cycle. In the initial stage of SAA amplification, the pathological alpha-Syn aggregates as seeds are adsorbed to the interface between the solid phase and the liquid phase with the maximum shear stress, greatly increasing the alpha-Syn aggregation efficiency, shortening the lag time in the initial stage, greatly shortening the amplification time, and solving the problems existing in the current alpha-Syn-SAA test.

The invention belongs to the technical field of animal model construction, and particularly relates to a mouse model based on alpha-synuclein mutation and a construction method and application thereof. The mouse Snca gene is subjected to site-specific modification and mutates at the site S129A, S129D or Y125F, an alpha-syn mutation animal model which does not need exogenous induction and can naturally develop typical PD pathology and behavior phenotypes is constructed, and the limitation of an existing model in the aspects of pathology reduction degree and experiment controllability is broken through.

Compounds comprising an amide-linked coumarin scaffold, compositions comprising same, and method of using such compounds and compositions to inhibit tubulin-associated unit (tau) protein aggregation or alpha-synuclein ( α-syn) protein aggregation in a subject having, or at risk for, tau protein aggregation or α-syn protein aggregation, respectively.

The application discloses expression regulation of alpha-synuclein and application thereof. The alpha-synuclein inhibitor is used for preparing a medicine, and the obtained medicine has the effects of preventing and treating anxiety caused by social isolation. Experiments prove that after the alpha-synuclein inhibitor is administered, the anxiety behavior of a model animal in a social isolation environment can be improved, and the alpha-synuclein inhibitor has a treatment effect on anxiety caused by social isolation. The alpha-synuclein inhibitor is selected from the following: 1) an ASO targeting SNCA mRNA coding alpha-synuclein; 2) a small-molecule compound targeting SNCA mRNA coding alpha-synuclein; or 3) an AAV interfering with the expression level of alpha-synuclein in a ventral hippocampal neuron.

The present invention relates to proteins, particularly antibodies such as anti-CD20 / anti-CD3 bispecific antibodies and anti α-synuclein antibodies, having monogalactosylated (Gi) and digalactosylated (G2) glycans. More particular, the present invention relates to galactosylation engineering to generate proteins with improved therapeutic properties, including proteins with increased titer. Further, the invention relates to a cell culture medium and a mammalian cell as well as methods using said cell culture medium and said mammalian cell for producing said proteins. Moreover, the present invention relates to the use of said antibodies as a medicament such as for the treatment of cancer, particularly cancer associated with B-cells, or Parkinson's disease.

The present invention relates to compounds of formula (I) for use as neuroprotective agents and / or in inhibiting formation of alpha-synuclein aggregates in vivo. The invention further relates to methods of inhibiting neurodegeneration and / or inhibiting formation of alpha-synuclein aggregates in vivo.

The disclosure pertains to conformational epitopes in alpha-synuclein, antibodies thereto and methods of making and using immunogens and antibodies specific thereto. In particular antibodies raised to cyclic compounds comprising at least 3 amino acids of EKTKEQ (SEQ ID NO: 1) selectively recognize misfolded oligomeric alpha-synuclein and are able to inhibit alpha-synuclein propagation and toxicity.

The present invention relates to a gene therapy for treating synucleinopathies. The present invention provides a novel α-Syn peptide variant and inhibits the formation of amyloid fibrils and degrades α-Syn aggregates, thereby exhibiting excellent preventive, ameliorative, and therapeutic effects on synucleinopathies.

The invention relates to the technical field of biomedical detection, in particular to an integrated micro-fluidic chip for detecting alpha-synuclein related to Parkinson's disease. The chip comprises a sample introduction module, a cell filtration module, a magnetic bead enrichment module, a mark detection module, a signal reading module and a microfluid driving control module which are integrated in a chip body to form a continuous microfluid channel system. Plasma separation is achieved through a double-layer filter membrane structure, target protein enrichment is completed through functionalized magnetic beads and a staged variable magnetic field strategy, a fluorescence labeling module is combined with a flow limiting structure and a constant-temperature cavity to achieve efficient signal reaction, and liquid directional transfer and automatic process control are completed in cooperation with positive and negative pressure cooperative driving. The chip has the advantages of compact structure, high processing efficiency, high sensitivity and the like, and is suitable for early screening and quantitative detection of Parkinson's disease.

A fusion molecule having phagocytosis-inducing activity is disclosed. The fusion molecule contains a first region capable of binding a TAM receptor and a second region capable of binding to a target substance of which aberrant accumulation is associated with or characteristic of diseases. The fusion molecule effectively clears and / or reduces and / or suppresses accumulated abnormal proteins, such as beta-amyloid, tau, alpha-synuclein, huntingtin, or prion, or the like. Uses of the fusion molecule are disclosed. The fusion molecule can be used for prevention or treatment of proteinosis caused by the abnormal accumulation of substances.

The application provides an application of scEMC10 in treatment and diagnosis of brain vascular endothelial cell aging, and relates to the technical field of biomedicine. The inventor finds that scEMC10 deficiency leads to brain microvascular endothelial cell aging; brain microvascular endothelial cells treated by scEMC10 can down-regulate beta-galactosidase, SASP and classic aging markers related to aging; after old mice and 5XFAD model mice of Alzheimer's disease are supplemented with scEmc10, the movement coordination ability and spatial cognitive ability of the mice can be obviously improved, and the relative content of the Parkinson's disease marker, phosphorylated alpha-synuclein, of the old mice can be obviously reduced, and the content of the tyrosine hydroxylase phosphorylation activity form can be increased. Therefore, scEMC10 can be used for treatment of brain microvascular endothelial cell aging, improvement of Alzheimer's disease and Parkinson's disease, and detection of brain microvascular endothelial cell aging as a marker.