30 results about "Tau phosphorylation" patented technology

The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β1-42.

The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.

The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β1-42.

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 relates to a pharmaceutical composition for the treatment of neurodegenerative disorders, comprising an effective amount of a tungsten (VI) compound, preferably tungstate, and more preferably sodium tungstate (Na2WO4). The pharmaceutical composition of the present invention can be used for the preventive and / or therapeutic treatment of neurodegenerative disorders in mammals (including humans), and especially in the preventive and / or therapeutic treatment of Alzheimer's disease and schizophrenia. The effect of sodium tungstate dihydrate on tau phosphorylation was evaluated in rat models of insulin resistance and type 1 diabetes. Therapeutic treatment of Tau-associated diseases from the present invention includes several advantages: GSK3 inhibition; specificity, since it reduces abnormal hyperphosphorylation of tau caused by nerve-specific proteins; efficacy; lack of toxicity; and low price.

Methods of screening for candidate compounds capable of inhibiting activity of fyn in phosphorylating tau protein at Y394 or binding to fyn to inhibit interaction with tau protein at Y394, including determining whether, and optionally the extent, the candidate compounds have these capabilities under conditions where fyn has these capabilities in the absence of the candidate compound. Methods of screening for substances capable of promoting dephosphorylation of tau protein by a phosphatase at a site of tau protein including contacting a candidate substance, the tau protein and a phosphatase capable of dephosphorylating the tau protein under conditions where the phosphatase is capable of dephosphorylating the site in absence of the candidate substance, where the kinase is fyn; determining whether, and optionally the extent, the candidate substance promotes dephosphorylation of the tau protein at the site; and selecting the candidate substance which promotes dephosphorylation of the tau protein the sites.

The present invention is directed to novel kinase inhibitors of general formula (I) and pharmaceutically acceptable salts thereof, and to the use of the kinase inhibitors of general formula (I) for treating diseases or disorders in which tau phosphorylation and cell cycle regulation is implicated, such as Alzheimer's Disease and cancer.

A method of inhibiting phosphorylation of the tau protein and / or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

The present invention relates to antibodies that -differentially -recognize- -multi- dimensional conformations- of- Ass- derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid ss 1-42.

Methods of diagnosing a tauopathy and predicting whether a subject will develop a tauopathy are provided. Also provided are antibody preparations that specifically bind to tau phosphorylated at tyr394 and / or tyr310. Methods of inhibiting tau phosphorylation in a cell and methods of treating a subject having a tauopathy are additionally provided. Methods of treating a subject at risk for a tauopathy are also provided. Additionally, non-human mammals comprising a transgene encoding an abl tyrosine kinase are provided. Also provided are methods of evaluating whether a compound inhibits development of a tauopathy.

A method of inhibiting phosphorylation of the tau protein and / or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.

The present invention was accomplished for the purpose of developing a method for effectively treating and / or preventing synucleinopathies, and is based on a discovery that an adiponectin receptor agonist suppresses α (alpha)-synuclein aggregation, tau phosphorylation and a decrease in proteasomal activity.The method of the present invention for treating and / or preventing neurodegenerative diseases includes a step of administering an effective dose of at least one effective element selected from a group consisting of: adiponectin as an adiponectin receptor agonist; a compound inducing expression of adiponectin; globular adiponectin; and a compound inducing expression of globular adiponectin. The present invention further provides a screening method of the adiponectin receptor agonist for treating and / or preventing neurodegenerative diseases.

The present invention relates to a composition comprising the mixed extract of mulberry and Poria cocos peel for preventing, improving or treating neurodegenerative disorders. The mixed extract of mulberry and Poria cocos peel which is the active ingredients contained in the composition of the present invention, has a memory improving activity through inhibiting of acetylcholine esterase and a neuroprotective effects and neuron protection by inhibiting the formation of beta amyloid and tau phosphorylation and promoting NGF production. Thus, the present invention may be useful as a pharmaceutical composition for preventing or treating degenerative neurological diseases, or as a health food for the above purpose.

We found that Andrographolide binds to GSK-3β:In so doing, andrographolide prevents changes in neuropathology in an Alzheimer's model, reducing Amyloid-β peptide levels, changing the ontogeny of hippocampus and cortex amyloid plaques, and reducing tau phosphorylation around Amyloid-β. Andrographolide recovers spatial memory functions in an Alzheimer's model. Andrographolide and its derivatives may be used to treat Alzheimer's disease.

The present invention relates to a pharmaceutical composition and a food composition for preventing or ameliorating degenerative neurological disease comprising Poria cocos peel extract for preventing, or treating neurodegenerative disorders. Poria cocos peel extract which is the active ingredients contained in the composition of the present invention, has a memory ameliorating activity through inhibiting of acetylcholine esterase and a neuroprotective effect and neuron protection by inhibiting the formation of beta amyloid and tau phosphorylation and promoting NGF production. Thus, the present invention may be useful as a pharmaceutical composition for preventing or treating degenerative neurological diseases, or as a health food for the above purpose.

The present invention provides methods and compositions for enhancing working memory impaired in a tau pathological condition associated with AD or Down's syndrome.

The present invention was accomplished for the purpose of developing a method for effectively treating and / or preventing synucleinopathies, and is based on a discovery that an adiponectin receptor agonist suppresses α (alpha)-synuclein aggregation, tau phosphorylation and a decrease in proteasomal activity.The method of the present invention for treating and / or preventing neurodegenerative diseases includes a step of administering an effective dose of at least one effective element selected from a group consisting of: adiponectin as an adiponectin receptor agonist; a compound inducing expression of adiponectin; globular adiponectin; and a compound inducing expression of globular adiponectin. The present invention further provides a screening method of the adiponectin receptor agonist for treating and / or preventing neurodegenerative diseases.

The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.

The invention discloses a method for inhibiting tau pathological prion transmission through mediation of adeno-associated viruses. The method comprises the following steps: constructing a recombinant adeno-associated virus; injecting the constructed adeno-associated virus into the right ventricle of a mouse in a ventricle injection manner; separating pathological tau, namely AD O-tau, extracted from the brain of an AD patient; and injecting the separated AD O-tau into the hippocampus of the mouse. Results show that rAAV9 can be used as an effective tool vector for delivering genes in brain tissues, over-expression of a PP2A gene is mediated through a virus vector, and dephosphorylation of tau is increased, so a molecular mechanism of tau pathogenesis is studied, the relationship between tau pathology aggregation and prion transmission and tau phosphorylation level and PP2A is defined, the feasibility of rAAV vector mediated gene therapy is prompted, the screening of drugs for inhibiting or reversing the generation, development and transmission of tau pathology can be facilitated, and a new strategy is provided for the treatment of such diseases.

The present invention relates to a pharmaceutical composition and a food composition for preventing or ameliorating degenerative neurological disease comprising Poria cocos peel extract for preventing, or treating neurodegenerative disorders. Poria cocos peel extract which is the active ingredients contained in the composition of the present invention, has a memory ameliorating activity through inhibiting of acetylcholine esterase and a neuroprotective effect and neuron protection by inhibiting the formation of beta amyloid and tau phosphorylation and promoting NGF production. Thus, the present invention may be useful as a pharmaceutical composition for preventing or treating degenerative neurological diseases, or as a health food for the above purpose.

The present disclosure provides methods to quantify tau phosphorylation at specific amino acid residues to predict time to onset of mild cognitive impairment due to Alzheimer's disease, stage Alzheimer's disease, guide treatment decisions, select subjects for clinical trials, and evaluate the clinical efficacy of certain therapeutic interventions.

The present invention is directed to novel kinase inhibitors of general formula (I) and pharmaceutically acceptable salts thereof, and to the use of the kinase inhibitors of general formula (I) for treating diseases or disorders in which tau phosphorylation and cell cycle regulation is implicated, such as Alzheimer's Disease and cancer.

Methods for screening for substances capable of modulating the phosphorylation of tau protein are disclosed, and in particular paired helical filament (PHF) tau, and the use of such modulators in the treatment of tauopathies. The assays and screening methods are based on the identification of new phosphorylation sites in PHF tau and new kinases and combinations of kinases as therapeutic targets, in particular the identification of casein kinase 1 as a kinase which phosphorylates tau protein.

The present invention provides methods and compositions for enhancing working memory impaired in a tau pathological condition associated with AD or Down's syndrome.

The present disclosure provides for using a blood sample to quantify tau phosphorylation at a particular amino acid residue to predict the time from the onset of mild cognitive impairment caused by Alzheimer's disease, staging Alzheimer's disease, guiding treatment decisions, and determining the onset of cognitive impairment caused by Alzheimer's disease. Methods of selecting subjects of a clinical trial and assessing the clinical efficacy of certain therapeutic interventions.