214 results about "Synuclein" patented technology

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 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 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 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 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.

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.

The invention relates to a method for detecting misfolded alpha-synuclein protein in a biological sample to determine the presence of synucleinopathies in an individual. The method provided by the present invention can also be used for differential diagnosis of Lewy fold synucleinopathies from MSA synucleinopathies as well as for monitoring of the disease progression in individuals. Moreover, a kit for detecting misfolded αSyn protein in biological samples is provided.

The present disclosure provides a compound of Formula I for use in a method of treating or preventing synucleinopathies comprising administering to a subject a therapeutically effective amount of the Compound (I): (I) or a pharmaceutically acceptable salt or hydrate thereof.

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.

Herein disclosed is configuring a layered receptor with at least one layer comprising graphene oxide and an biomarker binding layer configured to bind with a targeted biomarker, connecting a working electrode comprising carbon nanotubes (CNT) and a reference electrode to the layered receptor, and detecting events comprising the targeted biomarker binding layer with the biomarker binding layer, by measuring changes in impedance to a plurality of frequencies of an alternating current voltage signal applied through a patient's body fluid between the working electrode and the reference electrode. The layered receptor may further comprise a plurality of self-assembled layers, comprising, in sequence, a layer abutting the CNT and comprising a polymer and metal nanoparticles, a layer comprising an organosulfur, the graphene oxide layer and the biomarker binding layer. The biomarker binding layer may comprise Syn-211, LB509 or 5G4. The targeted biomarker may be alpha-synuclein. An implementation may report biomarker concentrations in real-time based on detected binding events.

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.

A system and method for protein detection are provided, configured to non-invasively identify proteins exhibiting specific structural conformations within a biological target. The system comprises a light source operable to irradiate the target at a predetermined pulse cycle, a sound detection device configured to capture acoustic signals generated via the photoacoustic effect, and an information processing unit that analyzes the detected acoustic signals to determine the presence or accumulation of a target protein. This technique facilitates early-stage detection of disease-associated proteins, such as amyloid-β and misfolded α-synuclein fibrils, without requiring complex imaging modalities or invasive biopsy procedures.

The invention relates to application of a fluorescence value of NEV / OEV in plasma in auxiliary identification of Parkinson's disease and multi-system atrophy. Comprising the following steps that NEVFmax / OEVFmax is used as a diagnostic index for auxiliary identification of PD and MSA, NEVFmax is the maximum value of an NEV reaction endpoint fluorescence signal obtained in an RT-QuIC experiment, and OEVFmax is the maximum value of an OEV reaction endpoint fluorescence signal obtained in the RT-QuIC experiment. Compared with the prior art, the kit has the advantages that the PD and the MSA are identified by combining the peripheral blood with the alpha-syn amplification technology for the first time, efficient identification of the PD and the MSA is realized, and the blank of identifying the two diseases by combining the exosome in the peripheral blood with the alpha-syn amplification technology is filled.

The present invention relates to the technical fields of radiopharmaceutical chemistry and clinical nuclear medicine, in particular to imidazothiadiazole compounds as well as a preparation method therefor and the use thereof. The compounds are shown as general structural formula (I). After being labeled with a suitable radioisotope, the compounds and derivatives thereof can perform nuclear medicine imaging on α-synuclein aggregates in the brain, so as to assist in clinical diagnosis of synuclein diseases including Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and some rare diseases.

The present invention relates to a composition for diagnosing Parkinson's disease, comprising a preparation for detecting a protein comprising GLUT3 in combination with one or more substances selected from the group consisting of USP14, alpha-synuclein, and AIMP2, or a gene encoding the protein. When using the composition for diagnosing Parkinson's disease and the diagnostic kit comprising the composition according to the present invention, it is possible to detect or diagnose Parkinson's disease by distinguishing Parkinson's disease patient groups by a simple blood test. Further, the present invention can be used as a pre-diagnosis for determining whether or not neurological examinations or brain image examinations are to be performed in a large hospital by preferentially applying to patients who exhibit premonition symptoms of Parkinson's disease such as anomalies, sleep disorders, and constipation. In addition, the compound can be used as a means for quantifying the treatment effect of Parkinson's disease.

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.

Diagnostic and therapeutic methods for neurodegenerative diseases. Are provided involving assaying abnormal proteins (hyperphosphorylated tau, α-synuclein, TDP-43) associated with neuronal turnover inhibition or promotion in patient samples. Abnormal protein expression and apoptotic activity are detected, aiding disease progression assessment. Therapeutically, a method is provided for treating neurodegenerative diseases, administering compounds promoting neuronal turnover or modulating proteins involved in the process. The invention extends to identifying suitable drugs, employing neuronal turnover induction, miRNA modulation, and protein activity inhibition or enhancement. The claims also encompass various species, tissues, and cultured cells. Furthermore, the invention is applicable to diverse neurodegenerative diseases with abnormal protein accumulation, presenting novel diagnostic and treatment approaches.

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.