374 results about "Tau protein" patented technology

Imaging agents of formula (I) and methods for detecting neurological disorders comprising administering to a patient in need compounds of formula (I) capable of binding to tau proteins and β-amyloid peptides are presented herein. The invention also relates to methods of imaging Aβ and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formula (I) and detecting the labeled compound associated with amyloid deposits and / or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disorders.

The present invention relates to methods of treating and preventing Alzheimer's Disease or other tauopathies in a subject by administering a tau protein, its immunogenic epitopes, or antibodies recognizing the tau protein or its immunogenic epitopes under conditions effective to treat or prevent Alzheimer's Disease of other tauopathies. Also disclosed are methods of promoting clearance of aggregates from the brain of the subject and of slowing progression of tangle-related behavioral phenotype in a subject.

Provided are electrokinetically-altered fluids (e.g., electrokinetically-altered gas-enriched fluids and solutions) comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures in an amount sufficient for treating an inflammatory neurodegenerative condition or disease (e.g., a taupathy) or at least one symptom thereof. The electrokinetically-altered fluids or therapeutic compositions and methods include electrokinetically-altered ionic aqueous fluids optionally in combination with other therapeutic agents. Particular aspects provide for modulating phosphorylation of tau protein. Particular aspects provide for regulating or modulating intracellular signal transduction associated with said inflammatory responses by modulation of at least one of cellular membrane potential and / or conductance, membrane proteins such as membrane receptors, including but not limited to G-Protein Coupled Receptors (GPCR), and intercellular junctions (e.g., tight junctions, gap junctions, zona adherins and desmasomes). Other embodiments include particular routes of administration or formulations for the electrokinetically-altered fluids and therapeutic compositions.

Novel indolocarbazole derivatives potentially useful for the treatment of dementias characterized by tau hyperphosphorylation [Alzheimer's disease (AD), frontal lobe degeneration (FLD), argyrophilic grains disease, subacute sclerotising panencephalitis (SSPE) as a late complication of viral infections in the CNS], and cancer.

The present invention provides compounds, or salts or solvates thereof, which can be used as probes for the imaging diagnosis of diseases in which tau protein accumulates, and compositions and kits comprising such compounds, or salts or solvates thereof. The present invention also provides a method for staining neurofibrillary tangles in brain samples, and a pharmaceutical composition for the treatment and / or prophylaxis of a disease in which β-sheet structure is the cause or possible cause.

The present invention is a composition and method for the prevention and treatment of a tauopathy. The composition of the invention includes N-terminal amino acid residues of the tau protein, which have been identified as being involved in toxic activation of a PP1 / GSK3 signaling cascade and inhibition of fast axonal transport in human tauopathies.

A method for identifying a desired binding agent that interferes with the interaction between a protein, protein fragment, polypeptide or a peptide and a binding surrogate. The method comprises combining the protein, protein fragment, polypeptide or peptide, the binding surrogate and a binding agent. Detecting a decrease in the interaction between the protein, protein fragment, polypeptide or peptide from the binding surrogate indicates that the binding agent interferes with the interaction. Proteins useful in the method include the tau protein phosphorylated at threonine (231), the Amyloid Precursor Protein (APP) phosphorylated at threonine (668 and cdc25 phosphorylated at threonine (48). Compounds identified by the method are useful in the treatment of Alzheimers' disease and cancer.

The invention relates to a pyrro-quinoline quinine (PQQ) sodium salt derivative and a preparation method thereof, belonging to the field of pharmacy. In the preparation method, PQQ is used as a raw material, and an acid-base neutralization reaction with PQQ is carried out in a basic solvent of sodium hydroxide to prepare the PQQ sodium salt derivative represented in the structural formula (I), wherein R1, R2 and R3 can be identical or different and respectively represents H, ammonium ion (NH3), potassium ion, sodium ion, magnesium ion, calcium ion or zinc ion, and at least one of R1, R2 and R3 is sodium ion. The invention has mild reaction conditions, easy product refining and purification, simple preparation steps and high yield more than 80%. The PQQ sodium salt derivative has the functions of inhibiting GSK-3 activity, reducing senile pigment formation in a transgenic mouse brain, reducing tau protein phosphorylation and the like. Thus, the PQQ sodium salt derivative can be medically used for treating senile dementia and other diseases.

The invention relates to translation enhancer elements that enhance translation of the gene encoding the human microtubule-associated tau protein and nucleic acid molecules that enhance translation of the gene encoding the human α-synuclein protein. The translation enhancer elements of the invention are useful in compositions and methods for identifying compounds for the prevention and / or treatment of neurodegenerative disease. The invention also includes in some aspects, vectors that include a translation enhancer element of the invention. The invention also includes the use of enhancer element containing vectors in methods to produce recombinant protein and in assays to identify compounds that modulate expression of tau protein or α-synuclein protein.

A transgenic animal, preferably a mouse, that expresses human antichymotrypsin (ACT) in brain tissues is provided, together with animal tissue-derived cell lines and progeny animals of said transgenic animal. Progeny are obtained by mating the transgenic animal with select animal strains used as models of Alzheimer's disease, related neurological disorders, or amyloidogenic diseases. Methods utilizing the parent and progeny animals and cells derived therefrom are disclosed for testing compounds for use as anti-inflammatory drugs, inhibitors of amyloidogenesis, and / or inhibitors of tau protein pathology associated with Alzheimer's disease, in the treatment of a variety of neurological diseases.

The present invention relates to methods and compositions for treating, preventing, and diagnosing Alzheimer's Disease or other tauopathies in a subject by administering an immunogenic tau peptide or an antibody recognizing the immunogenic tau epitope under conditions effective to treat, prevent, or diagnose Alzheimer's Disease or other tauopathies. Also disclosed are methods of promoting clearance of aggregates from the brain of the subject and of slowing progression of tau-pathology related behavioral phenotype in a subject.

The present invention relates to the development of a pharmacological non-human animal model that associates memory loss to histopathological features found in the brain of a subject having Alzheimer's Disease. In one embodiment, a four-week continuous infusion of a Fe2+, Aβ42 and buthionine sulfoximine (FAB) solution in the left ventricle of young adult Long-Evans rats induced memory impairment accompanied by increased hyperphosphorylated Tau protein levels in cerebrospinal fluid. Brains from treated animals displayed neuritic plaques, tangles, neuronal loss, astrogliosis and microgliosis in hippocampus and cortex. The present invention may be utilized in evaluating preventive, therapeutic and diagnostic means for neurologic diseases.

The present invention provides an antibody which specifically recognizes a CNS tau protein but not a peripheral tau protein. More specifically, the present invention provides an antibody obtainable by using a polypeptide comprising an amino acid sequence of a connective portion between the amino acid sequence encoded by Exon 4 of a gene encoding a tau protein and the amino acid sequence encoded by Exon 5 thereof as an epitope specific to the isoform of tau protein predominantly existing in central nervous tissues. The present invention further provides a method of detecting Alzheimer's disease and a reagent kit using the antibody.

The present invention relates to Tau protein relative polypeptide antigen and antibody. The specific polypeptide antigen of the present invention has the amino acid sequence of SEQ ID No. 1, and corresponding polyclonal or monoclonal antibody may be obtained in available method. The antibody of the present invention may be prepared into kit for detecting and diagnosing senile dementia.

Methods of treating Tau-associated diseases, preferably tauopathies, are described using epothilone D that exhibit good brain penetration, long half-life, and high selective retention in brain, and provides effective therapies in treating tauopathies including Alzheimer's disease.

This invention concerns affinity tools for oligomeric forms of tau protein. It relates to the field of neurodegeneration, more particularly to the field of tau-related diseases and tauopathy. The invention provides novel tau antibodies and antibody fragments, nucleic acids encoding such antibodies and antibody fragments, cell lines producing such antibodies and antibody fragments, antibody compositions, and kits for the detection of aggregated tau and for the diagnosis of diseases involving aggregated tau. The invention further provides methods for the detection of aggregated tau, for the diagnosis of diseases involving aggregated tau, and for the identification of compositions interfering with the formation and / or stability of tau aggregates.

Antibodies selective for pathological tau dimers and / or prefibrillar pathological tau oligomers, immunogenic peptides and epitopes of these antibodies, hydridomas producing these antibodies, uses of these antibodies, immunogenic peptides and epitopes in preparation of pharmaceutical compositions for the treatment of tauopathies, and uses of these antibodies, immunogenic peptides, epitopes and pharmaceutical compositions in the treatment of tauopathies are described. Also described are uses of these antibodies, immunogenic peptides, epitopes in diagnosis and monitoring of tauopathies.

The present invention provides an antibody which specifically recognizes a CNS tau protein but not a peripheral tau protein. More specifically, the present invention provides an antibody obtainable by using a polypeptide comprising an amino acid sequence of a connective portion between the amino acid sequence encoded by Exon 4 of a gene encoding a tau protein and the amino acid sequence encoded by Exon 5 thereof as an epitope specific to the isoform of tau protein predominantly existing in central nervous tissues. The present invention further provides a method of detecting Alzheimer's disease and a reagent kit using the antibody.

The present invention provides a quantitative immunoaffinity LC-MS / MS assay for detection and quantification of Tau protein in a biological sample.

The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain onone end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase toeffect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation / inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

Imaging agents of formulas (I)-(V) and methods for detecting neurological disorders comprising administering to a patient in need compounds of formulas (I)-(V) capable of binding to tau proteins and [beta]-amyloid peptides are presented herein. The invention also relates to methods of imaging A[beta] and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formulas (I)-(V) and detecting the labeled compound associated with amyloid deposits and / or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disorders. Formula (V) or a pharmaceutically acceptable salt thereof, and stereoisomers thereof, wherein: X25-X28 are each independently CH, CR11, or N; X29 is CH, N, O or S; X30 is CH, C, or N; X31-34 are each independently CH, CR12, CR13 or N; RII-RU are each independently H, halogen, hydroxy, nitro, cyano, ammo, alkyl, alkylaryl, alkylamino, alkylamine, arylamine, arylamino, alkoxy,- (O-CH2-CH2)n-, alkenyl, alkynyl, aryloxy, NRl0 COO alkyl, NRl0 COO aryl NR10 CO alkyl, NR10 CO aryl, COO alkyl, COO aryl, CO alkyl, CO aryl, aryl, cycloalkyl, cycloalkylamino, cycloalkylamine, bicyclic, saturated heterocycle and unsaturated heterocycle, wherein at least one carbon of R11-R13 is optionally replaced with N, Q, S, triazole, or halo, and, wherein at least one hydrogen is optionally replaced with halo, amine, amino, alkoxy, nitro, alkyl, alkenyL alkynyl, aryloxy, alkylaryl, alkylamino, alkylamine, NR 10COO alkyl, NR10 COO aryl, NR10 CO alkyl, NR10 CO aryl, COO alkyl, COO aryl, CO alkyl, CO aryl, aryl, cycloalkyl, cycloalkylamino, cycloalkylamine, bicyclic saturated heterocycle and unsaturated heterocycle, a leaving group, CN, OH or a radioactive isotope.

Pharmaceutical compositions comprising an effective amount of a tungsten (VI) compound, preferably of a tungstate salt, and more preferably of sodium tungstate (Na2WO4), are useful for the prophylactic and / or therapeutical treatment of neurodegenerative disorders in a mammal, including a human, in particular, for the prophylactic and / or therapeutical treatment of Alzheimer's disease or schizophrenia. The effect of sodium tungstate dihydrate on the phosphorylation of tau in a model of rat insulin resistance and in a model of type-1 diabetes has been assessed. The therapeutic treatment of tauopathies that derives from this invention involves several advantages: it targets a GSK3; specificity since it reduces the abnormal hyperphosphorylation of a neural specific protein, tau, efficacy, lack of toxicity, and low price.

The present invention discloses a transgenic fly that expresses the Dutch mutant version of the human Aβ42 peptide of human amyloid-β precursor protein (APP), and a double transgenic fly that expresses both the Tau protein and the human Aβ42Dutch peptide of human amyloid-β precursor protein (APP). The transgenic flies of the present invention provide for models of neurodegenerative disorders, such as Alzheimer's disease. The invention further discloses methods for identifying genetic modifiers, as well as screening methods to identify therapeutic compounds to treat neurodegenerative disorders using the transgenic flies.

The present invention relates to antibodies capable of differentially recognizing the multidimensional conformation of A[beta]-derived diffusible ligands, also known as ADDLs. The antibody of the present invention can distinguish the brain extracts of Alzheimer's patients and control humans, and can be used in methods for detecting ADDLs and diagnosing Alzheimer's disease. The antibody of the present invention also blocks the binding of ADDLs to neurons, the aggregation of ADDLs, and the phosphorylation of tau protein, and thus can be used in methods for preventing and treating diseases related to soluble oligomers of amyloid β1-42.

The invention relates to antibodies with a specificity to an abnormally truncated form of tau protein, which is conformationally different from normal tau, and does not bind to normal tau protein, conformationally different tau proteins (“tauons”) and diagnostic and therapeutical aspects in relation to Alzheimer's disease and related tauopathies.

Intranasal administration of insulin for a predetermined period prior to anesthesia significantly prevented anesthesia-induced tau hyperphosphorylation and cognitive impairment and enhanced brain insulin signaling in mice. Intranasal insulin thus provides a treatment for prevention of anesthesia-induced tau pathology and increased risk for tauopathies in surgical patients and may be administered to a subject prior to anesthesia, such as by administering several doses of intranasal insulin for several consecutive days prior to any anesthesia.

The invention is directed to methods of treatment of Alzheimer's disease and other tauopathies, via the administration of antibodies having specificity to abnormal forms of tau protein, the antibodies showing no binding and / or reactivity to a normal tau protein and being administered under conditions and in amounts effective to prevent or treat Alzheimer's disease or other tauopathies. In certain embodiments, the antibodies are selective for soluble truncated tau protein truncated at (i) its C-terminus after the glutamic acid residue Glu391, or (ii) at the aspartic acid residue Asp421, or (iii) at its N-terminus at the aspartic acid residue Asp13, or (iv) a combination of (i)-(iii). Further aspects of the invention are directed to the administration of an immunogen comprising an abnormal tau, preferably a soluble truncated tau.

Provided herein is an isolated antibody or antigen-binding fragment that specifically binds tau, the antibody or fragment comprising a heavy chain variable (VH) region and a light chain variable (VL) region having amino acid sequences set forth herein. Also provided are methods of preventing or treating a tauopathy in a subject, comprising administering to a human in need of therapy for a tauopathy with one or more antibodies or fragments as described herein, wherein the antibodies or antigen-binding fragment are administered under conditions and in an amount effective to prevent or treat the tauopathy.

The present invention discloses a transgenic fly that expresses the Italian mutant version of the human Aβ42 peptide of human amyloid-β precursor protein (APP), and a double transgenic fly that expresses both the Tau protein and the human Aβ42Italian peptide of human amyloid-β precursor protein (APP). The transgenic flies of the present invention provide for models of neurodegenerative disorders, such as Alzheimer's disease. The invention further discloses methods for identifying genetic modifiers, as well as screening methods to identify therapeutic compounds to treat neurodegenerative disorders using the transgenic flies.

The application relates to an immoalditol compound for selectively inhibiting glycosidases, a prodrug thereof and a pharmaceutical composition comprising the compound or the prodrug The application also relates to the use of the immoalditol compound for treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc Such diseases and disorders include neurodegenerative diseases, tauopathy, cancers, and cardiac disorders