347 results about "Tau protein" patented technology

The invention discloses bifidobacterium breve and application thereof in relieving Alzheimer's disease, and belongs to the technical field of probiotics. The preparation method comprises the following steps: separating 18 bifidobacterium strains from feces of children aged 0-3 years old, analyzing and identifying the 18 bifidobacterium strains including bifidobacterium longum, bifidobacterium breve and bifidobacterium animalis, and screening out the bifidobacterium breve LE4 with potential Alzheimer's disease relieving capacity through in-vitro oxidation resistance and LPS (Lipopolysaccharide) removal capacity. The method comprises the steps of behavioral experiments (nesting experiments, open field experiments and water maze experiments), histopathologic analysis, molecular biological detection and the like. The multi-target AD intervention effects of improving the cognitive function, reducing A beta deposition and tau protein phosphorylation, relieving neuroinflammation, enhancing synaptic plasticity, repairing intestinal barriers, adjusting intestinal flora and metabolites and the like of the LE4 strain are comprehensively evaluated, and a new strategy is provided for promoting AD micro-ecological treatment.

The invention belongs to the technical field of biological detection, and relates to an antibody composition aiming at pTau217 protein detection and application thereof, and the antibody composition aiming at pTau217 protein detection comprises a target pTau217 protein antibody and a target Tau protein C-terminal antibody. Meanwhile, based on the antibody composition aiming at pTau217 protein detection, the invention further provides a kit for early diagnosis of the Alzheimer's disease. The invention provides an antibody composition aiming at pTau217 protein detection, which is stronger in detection specificity and higher in sensitivity, and an application of the antibody composition.

The invention discloses a tree shrew Alzheimer's disease modeling method. The method comprises the following specific steps: mixing an ethanol solution of Microcystin-LR with the concentration of 0.5 [mu] g / [mu] l with an amaninic acid solution, and injecting 2 [mu] l to Meynert basal nuclei on the two sides of a tree shrew respectively; and after drug administration is finished, normally feeding for 2 weeks to finish Alzheimer's disease modeling. The method comprises the following steps: under a sterile condition, sucking 200 microliters of sterile normal saline, adding the sterile normal saline into a small bottle containing 1mg of amanitine, repeatedly blowing and beating to completely dissolve the amanitine, and preparing a solution with the concentration of 5mu g / microliter; the Microcystin-LR solution is a product purchased in the market. According to the invention, a mixed solution of MC-LR (0.1 [mu] g) and IBO solution (3 [mu] g) is respectively injected to Meynert basal nuclei on both sides of the tree shrew, and a stable tree shrew AD model can be established after 2 weeks. After the medicine is administrated for 3 days, tree shrews have AD behavior expressions, such as drooping spirit and reduced activity; after two weeks, the tree shrew brain shows AD typical pathological expressions such as A beta deposition, increase of expression levels of multiple phosphorylation sites of Tau protein and the like.

The invention relates to an in vitro method for detecting a tau protein or fragment thereof in a saliva sample using a specific binding molecule, such as an antibody, directed to key epitopes of tau. The invention may find applications in diagnostics of tauopathies.

The present invention relates to a pharmaceutical composition for the prevention or treatment of degenerative brain diseases, comprising selexipag or a pharmaceutically acceptable salt thereof as an active ingredient. Selexipag inhibits the expression and production of pro-inflammatory or inflammatory cytokines in brain tissue, inhibits the activity of microglia or astrocytes, inhibits NLRP3 inflammasome activity and CDK6 expression, reduces amyloid plaques, increases the expression of the amyloid beta-degrading enzyme IDE, and inhibits the hyperphosphorylation of tau protein and the expression of tau kinase, and thus can be effectively used as a novel therapeutic agent for the prevention or treatment of degenerative brain diseases, cognitive disorders, learning disabilities, or memory disorders.

The present application belongs to the technical field of biomedicine, and more particularly, relates to an antibody or an antigen-binding fragment thereof capable of specifically binding to p-tau 217, and a multi-specific molecule, a pharmaceutical composition, and a kit comprising same. The present application further relates to use of the antibody or antigen-binding fragment thereof in preparing a kit or a drug. A monoclonal antibody (for example, 2A7 antibody) according to the present application has a high clinical application value in the detection and prevention of AD and the treatment of AD and other tau protein diseases.

The invention relates to a Tau protein detection kit with double antibody sandwich coupled DNAzyme and application thereof, and relates to the technical field of biological detection, the Tau protein detection kit comprises a first antibody coupled with a first constituent part of DNAzyme with catalytic activity, a second antibody coupled with a second constituent part of DNAzyme with catalytic activity, a fluorescent probe and a reaction buffer solution. The detection method provided by the invention can accurately capture the tiny signal of Tau protein, and provides powerful support for early diagnosis of neurodegenerative diseases such as Alzheimer's disease and the like.

Disclosed are protein-like polymers and uses thereof. The protein-like polymers generally comprise a polymer of formula (FX1). The polymer of formula (FX1) in some aspects comprises a peptide that (i) inhibits aggregation of, (ii) accelerates aggregation of, (iii) binds to, and / or (iv) mimics: (a) at least a portion of Tau protein, and / or (b) at least a portion of microtubulin protein.

The invention belongs to the technical field of biological medicine, and particularly relates to an extracellular vesicle drug delivery system, a preparation method thereof and application of the extracellular vesicle drug delivery system in treatment of Alzheimer's disease. According to the invention, one or more of stilbene glucoside, emodin, kaempferol, resveratrol and quercetin are used for regulating and controlling the expression of miRNA (micro Ribonucleic Acid) related to the disease progress in the extracellular vesicles, and the result shows that one or more of miR-let-7c-5p, miR-486-5p, miR-132-3p, miR-160b and miR-129-5p is remarkably up-regulated, and one or more of miR-342-3p, miR-16-5p and miR-125b-5p is remarkably down-regulated. The regulated extracellular vesicles can be used for treating Alzheimer's disease, relieving Tau protein abnormal phosphorylation, reducing amyloid protein beta deposition, inhibiting microglial cell activation, protecting neuronal cells and relieving memory deficits.

The invention discloses application of ginsenoside Rg5 in preparation of a medicine for treating Alzheimer's disease and an evaluation method, and relates to application of ginsenoside Rg5 in preparation of a medicine for treating Alzheimer's disease. The medicine improves A beta deposition, tau protein phosphorylation and neuron damage by adjusting the intestinal flora structure and metabolite level, and is used for relieving the pathological process of the Alzheimer's disease. The invention has the characteristics of multi-target effect, nerve protection, inflammation resistance and oxidation resistance.

The invention discloses application of astrocyte-derived extracellular vesicles carrying Tau in auxiliary diagnosis of progressive suprakaryotic paralysis, and belongs to the technical field of biomedicine. The specific Tau protein antibody and the anti-glutamic acid transporter 1 antibody are labeled by fluorescence, astrocyte-derived extracellular vesicles carrying Tau in the plasma are accurately detected, PSP patients, PD patients and healthy people can be accurately distinguished by analyzing the concentration of astrocyte-derived EVs carrying Tau in the plasma, and the kit has the advantages of high sensitivity, high sensitivity, high sensitivity and the like. An efficient PSP diagnosis biomarker and a diagnosis model are provided, and a new experience method and technical support are provided for PSP diagnosis and identification.

The invention provides a circular RNA circ0004801 and an application of the circular RNA circ0004801 in treatment of an Alzheimer's disease. The nucleotide sequence of the circular RNA circ0004801 is as shown in SEQ ID NO: 1 (Sequence Identity Number 1). The expression of the circular RNA circ0004801 in the hippocampal tissue of the AD mouse is obviously up-regulated, and the circular RNA circ0004801 is used as a'sponge 'of miR-7688-5p and plays a role by adjusting the TTBK1 expression and tau phosphorylation level. By knocking down the circular RNA circ0004801, the spatial learning and memory of a 3 * Tg mouse can be obviously improved, and the tau protein phosphorylation level of a hippocampus region and the NFTs density of a hippocampus DG region can be obviously reduced. Therefore, the circular RNA circ0004801 and the miR-7688-5p can be used as new targets for treating the AD (Alzheimer's disease). According to the invention, it is found for the first time that circular RNA circ0004801 regulates TTBK1 through a ceRNA mechanism, so that excessive phosphorylation of tau is driven, and a new molecular target is provided for AD early intervention treatment based on circRNA and miRNA.

The invention relates to the technical field of gene editing, in particular to a construction method of an Alzheimer's disease model pig based on endogenous multi-gene editing. According to the present invention, pegRNA and nick-sgRNA efficiently targeting pig APPKM652 / 653NL, PSEN1M143L and TAUP300L sites are designed based on the PE technology, and an optimized editing system is adopted to achieve synchronous and accurate editing of pig endogenous three gene sites so as to successfully obtain the Alzheimer's disease model pig based on endogenous multi-gene synchronous editing, such that the Alzheimer's disease model pig can be used for screening the Alzheimer's disease; the cloned pig can reproduce Alzheimer's disease characteristic A beta deposition gene and Tau protein excessive phosphorylation double pathological phenotypes, can be applied to Alzheimer's disease drug screening, pathological mechanism research, target verification, biomarker development and the like, and has a wide application prospect.

The invention discloses a brain-derived Tau protein single-molecule fluorescence immunoassay detection kit and a use method, the kit provided by the invention is composed of a BD-Tau magnetic bead reagent coated with a capture antibody, a BD-Tau calibrator, a BD-Tau quality control product, a biotinylated BD-Tau Detector reagent for detecting the antibody, a BD-Tau SBG reagent, an RGP reagent and a BD-Tau sample diluent, the magnetic bead concentration of the BD-Tau magnetic bead reagent is 0.04 mg / mL-0. 08mg / mL of carboxyl magnetic beads, the carboxyl magnetic beads are coated with Tau J5.H3 coated antibodies, the detection antibody in the BD-Tau Detector reagent of the biotinylated detection antibody is Tau12, the concentration of the detection antibody is 0.3 mu g / mL-0. 8mu g / mL, and the concentration of SBG in the BD-Tau SBG reagent is 40 pM-60 pM; the kit disclosed by the invention can be used by adopting any one of a one-step method, a two-step method or a three-step method to detect the content of the BD-Tau protein in a plasma sample, the detection limit is 0.050 pg / mL, and the detection range is 0.050 pg / mL-150 pg / mL; according to the invention, the specificity, accuracy and reliability of determination of the Alzheimer's disease are improved, and the problems of early diagnosis and early screening of the Alzheimer's disease are solved.

The present invention relates to a composition for preventing, alleviating or treating cognitive disorders or Alzheimer's disease, comprising a Lactobacillus delbrueckii subsp. Lactis strain as an active ingredient. The present invention provides a composition for preventing, alleviating or treating cognitive disorders or Alzheimer's disease (AD), comprising a Lactobacillus delbrueckii subsp. Lactis strain as an active ingredient. The strain of the present invention has excellent effects of reducing amyloid beta protein (A beta) or tau protein (Tau) and improving cognitive function, and thus can be usefully used as a composition for preventing, alleviating or treating cognitive impairment or AD.

The invention relates to neurodegenerative disorders, and particularly to diagnostic and prognostic methods, apparatus and kits for neurodegenerative disorders, such as mild cognitive impairment (MCI), Alzheimer's disease, Parkinson's disease, Huntington's disease or Motor Neurone disease. The invention also extends to methods of detecting novel biomarkers, and methods for treating patients diagnosed or prognosed with a neurodegenerative disorder. A mathematical correlation between the concentrations of Tau protein and T14 peptide is found in samples from healthy subjects without a mood disorder, but not in samples from subjects having neurodegenerative disorders or a predisposition thereto.

Alzheimer's disease, the most common cause of dementia in older individuals, is a debilitating neurodegenerative disease for which there is currently no cure. In the past, AD could only be definitively diagnosed by brain biopsy or upon autopsy after a patient died. These methods, which demonstrate the presence of the characteristic plaque and tangle lesions in the brain, are still considered the gold standard for the pathological diagnoses of AD. However, in the clinical setting brain biopsy is rarely performed and diagnosis depends on a battery of neurological, psychometric and biochemical tests, including the measurement of biochemical markers such as the ApoE and tau proteins or the beta-amyloid peptide in cerebrospinal fluid and blood. The present invention discloses and describes panels of makers that are differentially expressed in the disease state relative to their expression in the normal state and, in particular, identifies and describes panels of makers associated with neurocognitive disorders. Such biomarker panel might have considerable value in triaging patients with early memory disorders to yet more specific but more invasive and costly approaches such as molecular markers in CSF and on PET imaging in clinical trials and possibly in clinical practice.

The present invention relates to a human ectoderm derived brain cell characterized by the following features: (1) the intron between exons 10 and 11 of the MAPT gene encoding the Tau protein has been removed by genome-editing from one or both allele(s); and (2) at least one of the alleles of the MAPT gene of (1) carries at least one mutation enhancing Tau aggregation and at least one mutation enhancing nucleation of Tau aggregation; or (3) one allele of the MAPT gene as defined in claim 1(1) carries at least one mutation enhancing Tau aggregation, preferably in exon 10, and the other allele carries at least one mutation enhancing nucleation of Tau aggregation, preferably in exon 11.

The invention belongs to the technical field of biological medicines, and provides application of an ILDR3 gene and / or protein in preparation of medicines and diagnostic products for preventing and / or treating Tau-related diseases. The ILDR3 provided by the invention is a key therapeutic target of Tau-related diseases, and can simultaneously intervene a plurality of core links of Tau pathology, including promotion of Tau protein degradation, inhibition of excessive phosphorylation and blocking of abnormal aggregation of Tau protein. Test data show that expression of the ILDR3 in Tau related diseases is reduced, Tau pathology and cognitive impairment are aggravated by knocking out the ILDR3, and learning and memory functions of a Tau pathology model are remarkably improved and nerve injury is relieved by over-expression of the ILDR3. Therefore, the ILDR3 gene and / or protein can be applied to preparation of drugs and diagnostic products for preventing and / or treating Tau-related diseases.

To provide a composition and a method for reducing or destroying aggregation of Tau protein in a subject, for reducing Tau protein, and / or for reducing excessive and / or abnormal phosphorylation of Tau protein.SOLUTION: The problem is solved by a composition comprising the peptide according to claim 1.SELECTED DRAWING: None

The invention belongs to the technical field of medicines, and particularly relates to novel application of a medicine for intervening an APT2 target spot. The invention provides application of a medicine for intervening in an APT2 target spot in preparation of a medicine for preventing and / or treating Tau protein palmitoylation modification reduction related diseases. The learning and memory ability of an Alzheimer's disease model mouse in which the APT2 gene is knocked out or an APT2 inhibitor is injected is improved, the tangling aggregation and neuroinflammation of Tau protein are relieved, and the expression of protein related to synaptic function is increased. Experiments show that APT2 serving as a potential target spot for treating Alzheimer's disease has a remarkable effect of improving symptoms of neurodegenerative diseases, a new direction is brought to treatment of Alzheimer's disease, development of treatment of other Tau protein palmitoylation modification reduced related diseases is promoted, and the application has a wide prospect.

The present invention relates to a novel saturated heterocycle-substituted heteroaryl-carbonohydrazonoyl dicyanide compound or a pharmaceutically acceptable salt thereof, a preparation method therefor, and a pharmaceutical composition comprising same as an active ingredient for preventing or treating neurological diseases. The saturated heterocycle-substituted heteroaryl-carbonohydrazonoyl dicyanide compound of the present invention inhibits the aggregation or hyperphosphorylation of tau protein and / or TDP-43, and thus can be used for preventing and treating neurological diseases including tauopathy and TDP-43 proteinopathy.

This invention belongs to the field of biosensing and detection technology, specifically disclosing a Tau protein electrochemiluminescent aptamer sensor, its preparation method, and its application. The sensor uses a CsPbBr₃@PVP / Au composite material as the electrochemiluminescent substrate. A Tau protein-specific aptamer is immobilized on the substrate surface via Au-S bonds, and non-specific adsorption sites are blocked with 6-mercapto-1-hexanol. The CsPbBr₃@PVP / Au composite material is prepared by encapsulating CsPbBr₃ with PVP and then combining it with Au NPs. This invention utilizes the coordination passivation effect of PVP and CsPbBr₃ to significantly improve the aqueous stability and electrochemiluminescence efficiency of perovskite nanocrystals. Combined with the anchoring effect of AuNPs and the specific recognition effect of aptamers, it achieves ultrasensitive detection of Tau protein with a detection limit as low as 0.80 fg / mL. Furthermore, it exhibits excellent selectivity, stability, and detection accuracy in complex biological samples such as cerebrospinal fluid, providing a novel and efficient detection platform for the early diagnosis of Alzheimer's disease and showing promising clinical application prospects.

The present invention provides a compound having O-GlcNAcase inhibitory activity and capable of reducing tau protein phosphorylation in vivo, and a pharmaceutical composition comprising the compound for treating or preventing diseases caused by tau protein hyperphosphorylation.

The invention discloses application of a gastrodia elata active ingredient in preparation of a medicine for preventing and treating Alzheimer's disease, and relates to the technical field of medicine and biologication.The key point of the technical scheme is that the gastrodia elata active ingredient comprises specific miRNA Gas-miR04-3p and Gas-miR19-5p obtained by screening from gastrodia elata, and the miRNA can be used for preparing the medicine for preventing and treating Alzheimer's disease through a targeted JNK3 signal channel. The occurrence of Tau protein excessive phosphorylation and cell apoptosis in the Alzheimer's disease model is regulated and controlled. The invention verifies that Gastrodia elata specific miRNA (Ribonucleic Acid) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) and Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia elata) of Gastrodia elata (Gastrodia

This method for producing a brain organoid including aggregated tau protein comprises: a step (a) for culturing pluripotent stem cells in the presence of SMAD inhibitor to form embryoid bodies; a step (b) for embedding the embryoid bodies in an extracellular matrix and three-dimensionally culturing the embryoid bodies in the presence of SMAD inhibitor and GSK3β inhibitor to form an organoid that includes neural precursor cells; a step (c) for removing the organoid from the extracellular matrix and suspension-culturing the organoid in the presence of LIF to form a brain organoid; a step (d) for forcing the brain organoid to express a modified MAPT gene; and a step (e) for further suspension-culturing the brain organoid after step (d) to obtain a brain organoid having an aggregated tau protein.

The present invention relates to the technical field of biological medicines. Disclosed are a combined detection kit for assisting in diagnosis of Alzheimer's disease and the use. Disclosed is the combined use of at least four of amyloid β-proteins, phosphorylated Tau proteins, biomarkers of neurodegeneration or neuron damage, and biomarkers related to neuroimmune disorder, synaptic dysfunction and blood brain barrier alternation in assisting in diagnosis of Alzheimer's disease. Compared with single-biomarker detection existing in the market and the combined detection using a small number of markers disclosed in some published patents, the marker combined detection provided by the present invention achieves a higher specificity or sensitivity. The present invention establishes a brand-new algorithm model, and both AD scale rating and brain function imaging diagnosis result rating are incorporated into the algorithm model for cooperative diagnosis; under the condition of a 95% specificity, the diagnosis sensitivity thereof can reach 95%, which is far higher than that of similar products in the market.

The present invention provides an antibody or antigen-binding fragment thereof that: (a) specifically binds 4R tau protein isoforms in a physiological sample; or (b) specifically binds 3R tau protein isoforms in a physiological sample. The present invention further provides nucleic acids and vectors encoding such an antibody or antigen-binding fragment, as well as host cells comprising such nucleic acids and vectors. The antibodies and fragments may be used in treating and diagnosing tauopathies.

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

This invention discloses a polypeptide that inhibits the desimilarization activity of tau protein and its applications, belonging to the field of biomedical technology. The polypeptide of this invention is tau. 438 The peptide is obtained through endogenous tau protein synthesis. The peptide provided by this invention can inhibit tau protein desimulation and increase tau mimicry, exhibiting high specificity and safely and effectively improving cognitive and memory function in AD model mice.