191 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 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 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 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.

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 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

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.

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.

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.

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 invention relates to methods and materials for use in treating neurodegenerative diseases associated with pathological protein aggregates and provides fusion proteins comprising: (i) a first portion comprising a sequence of a protein which aggregates pathologically in neurodegenerative disease, such as tau protein, and (ii) a second portion comprising a RING-type E3 ubiquitin ligase, a component of a RING-type E3 ubiquitin ligase complex, or a domain of either. These fusion proteins have utility in selectively or preferentially targeting pathogenic protein aggregates for degradation.

Disclosed herein are antisense compounds and methods for reducing tau protein mRNA and protein expression. Such methods, compounds, and compositions are useful for treating, preventing, or ameliorating tau-related diseases, disorders, and conditions.

The invention discloses a nerve cell injury repairing composition and a preparation method and application thereof, and belongs to the technical field of biological medicines.The nerve cell injury repairing composition is prepared from adipose tissue-derived stem cell exosome, quercetin, beta-pinene, juniperus formosana-sourced defensin and polyethylene glycol, a proper amount of PBS buffer solution with the pH value being 7.5 is dissolved, the amino acid sequence of the defensin is shown as SEQ ID NO.1 or SEQ ID NO.2, and the amino acid sequence of the defensin is shown as SEQ ID NO.2; the nerve cell injury repairing composition is obtained. The defensin derived from juniperus formosana is introduced to improve the problem of nerve cell injury, so that the excessive phosphorylation level of tau protein can be remarkably improved, and the activity of nerve cells can be improved within a certain time, thereby repairing the nerve cell injury. Meanwhile, the adipose-derived mesenchymal stem cell exosome, quercetin and beta-pinene are compounded, so that the anti-inflammatory and anti-oxidation effects can be achieved, and the function of nerve cell injury is further promoted.

Methods of differentiating and quantifying modifications in the tau protein in bio-fluids to detect, classify, and treat a plurality of tauopathies are disclosed. The disclosed methods include liquid chromatographic mass spectrometric analyses on isolated tau protein fragments to identify and quantify deamidated or isomerized asparagines or aspartic acids indicative of a neuropathology associated with a tauopathy.

The present invention relates to antibody-based molecules that are capable of preferentially and selectively binding to the C-terminal di-phosphorylated {p}Ser396 / {p}Ser404 Tau peptide as well as to the {p}Ser404 Tau peptide and the non-phosphorylated Tau peptide, but does not bind to the {p}Ser396 Tau peptide. Such antibody-based molecules are useful to detect pathological Tau protein conformer if present in a biological sample, especially in conjunction with the diagnosis and / or treatment of Alzheimer's disease or other Tauopathy, and thus provide a diagnostic for Alzheimer's disease and other Tau pathologies. The antibody-based molecules of the present invention also have particular utility as prophylactic and therapeutic molecules for the treatment and / or prevention of Alzheimer's disease and related tauopathies.

This invention belongs to the field of biochemistry technology, and relates to a near-infrared chemiluminescent probe responsive to tau protein, its preparation method, and its application. The preparation method of the near-infrared chemiluminescent probe includes the following steps: adding compound (I), compound (II), a catalyst, and an alkaline additive to a first solvent for reaction to obtain compound (III); adding compound (III), compound (IV), and piperidine to a second solvent for reaction to obtain compound (V); adding compound (V) and trifluoroacetic acid to a third solvent for reaction to obtain compound (VI); and adding compound (VI), compound (VII), and an acid compound to a fourth solvent for reaction to obtain the near-infrared chemiluminescent probe. The chemiluminescent probe of this invention exhibits high selectivity and efficient chemiluminescence capability, providing a promising tool for the diagnosis of Alzheimer's disease (AD). Its structural formula is: [Insert structural formula here].

The invention relates to a kit for combining markers P-tau181 and T-tau as well as a preparation method and application of the kit, and relates to the technical field of immunodetection. The kit comprises a first reagent and a second reagent, the first reagent comprises a magnetic bead working solution and a magnetic microsphere coated with a Tau polyclonal antibody; and the second reagent comprises a labeled antibody diluent and an acridinium ester labeled anti-Tau antibody. According to the invention, high-specificity anti-P-tau181 and anti-T-tau antibodies are adopted, one-time sampling can be realized, and the values of P-tau181 and T-tau proteins in human serum, plasma or urine samples can be detected at the same time; after the kit is adopted for 8 minutes, a result can be obtained, the repeatability is within 5%, the lowest detection limit of P-tau181 is 0.96 pg / ml, and the lowest detection limit of T-tau is 1.08 pg / ml.

The invention belongs to the technical field of biochemistry, and relates to a near-infrared chemiluminescence probe responding to tau protein as well as a preparation method and application of the near-infrared chemiluminescence probe. The preparation method of the near-infrared chemiluminescence probe comprises the following steps: adding a compound (I), a compound (II), a catalyst and an alkaline additive into a first solvent for reaction to obtain a compound (III); adding the compound (III), the compound (IV) and piperidine into a second solvent for reaction to obtain a compound (V); adding the compound (V) and trifluoroacetic acid into a third solvent for reaction to obtain a compound (VI); and adding the compound (VI), the compound (VII) and an acid compound into a fourth solvent for reaction to obtain the near-infrared chemiluminescence probe. The chemiluminescence probe provided by the invention has high selectivity and efficient chemiluminescence capability, and provides a potential tool for diagnosis of AD diseases. The structural formula is shown in the specification.

The application relates to the technical field of monoclonal antibodies, and specifically discloses an anti-p-Tau181 antibody and a preparation method and application thereof. The preparation method of the anti-p-Tau181 antibody comprises the following steps: taking a p-Tau181 polypeptide IPAKTPPAPK(pT)PPSSGEPPK as an immunogen, injecting the immunogen into experimental animals to perform an immune response, and obtaining spleen lymphocytes of the experimental animals; taking myeloma cells and the spleen lymphocytes to perform mixed culture to obtain fusion cells; culturing the fusion cells, obtaining supernatant, and performing ELISA detection; the polypeptide used for detection is the p-Tau181 polypeptide; taking the hybridoma cell strain with a positive detection result to perform counter screening with a p-Tau217 polypeptide, a p-Tau231 polypeptide and t-tau protein; screening a positive clone which has a reaction to the p-Tau181 polypeptide and has no reaction to the p-Tau217 polypeptide, the p-Tau231 polypeptide and the t-tau protein; performing multiple cloning screening; obtaining a hybridoma cell strain which can secrete antibodies every time; and taking the antibodies secreted by the hybridoma cell strain as the anti-p-Tau181 antibody. The anti-p-Tau181 antibody can be specifically combined with the p-Tau181, and thus can be used for detecting Alzheimer's disease.

The invention provides a pyridine derivative and a preparation method and application thereof, a Tau protein aggregate probe and a preparation method and application thereof, and relates to the technical field of ligands of protein aggregates. The pyridine derivative provided by the invention has an indole combined quinoline structure, has high selectivity, high specificity and high affinity to Tau protein, can be used as a selective ligand of a Tau protein aggregate, provides a diagnostic tool and a treatment strategy for neurodegenerative diseases such as Alzheimer's disease, and has broad application prospects. The method has potential value for early diagnosis, disease progress monitoring and treatment effect evaluation of neurodegenerative diseases.

The invention discloses a preparation method of a p-tau231 monoclonal antibody, the p-tau231 monoclonal antibody and an antibody variable region, and relates to the technical field of antibodies, the preparation method comprises the following steps: polypeptide design and synthesis: designing and synthesizing a phosphorylated polypeptide and a non-phosphorylated control polypeptide based on the 224th-238th amino acid sequence of tau protein, the phosphorylated polypeptide sequence is CKKVAVVRT (p) PPKSPSS, the phosphorylated polypeptide sequence is CKKVAVVRT (p) PPKSPSS, the phosphorylated polypeptide sequence is CKKVAVVRT (p) PPKSPSS, and the non-phosphorylated control polypeptide sequence is CKKVAVVRT (p) PPKSPSS; threonine (Thr231) at the 231st site is subjected to phosphorylation; the sequence of the non-phosphorylated polypeptide is CKKVAVVRTPPKSPSS, and the sequence of the non-phosphorylated polypeptide is Immunogen coupling: introducing cysteine residues to the N end of the phosphorylated polypeptide, and connecting the phosphorylated polypeptide with carrier protein KLH through a sulfydryl chemical coupling method to form an immunogen compound; and preparation of the conjugate for detection: introducing cysteine residues to the N ends of the phosphorylated polypeptide and the non-phosphorylated polypeptide, and respectively coupling with a carrier protein BSA to form the antigen complex for detection. The p-tau231 monoclonal antibody prepared by the technical scheme of the invention can be specifically combined with a p-tau231 antigen, has no specific reaction with non-phosphorylated polypeptide and tau polypeptide, and can be applied to early diagnosis of AD (Alzheimer's disease).

Disclosed are compositions and methods for treating Alzheimer's disease or for use in treating Alzheimer's disease. Also disclosed are compositions and methods for treating or for use in treating a neurodegenerative disorder characterized by the presence of tau protein aggregates. Furthermore, disclosed are compositions and methods for reducing tau protein aggregates or for use in reducing tau protein aggregates.