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64 results about "Hyperphosphorylation" patented technology
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Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signaling mechanisms used by the cell to regulate mitosis. When these mechanisms fail, developmental problems or cancer are a likely outcome. The mechanism appears to be largely conserved throughout eukaryote species.
Animal model simulating neurologic disease
InactiveUS20050102708A1Compounds screening/testingPeptide/protein ingredientsPharmacometricsButhionine sulfoximine
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.
Owner:SAMARITAN PHARMA +1
Compounds and Combinations Thereof for Inhibiting Beta-Amyloid Production and Methods of Use Thereof
InactiveUS20080058330A1Reduce productionLow productionBiocideNervous disorderAlzheimer's Disease Amyloid ProteinMedicine
Provided are compounds which can be used in combination for treating diseases associated with a condition associated with cerebral accumulation of Alzheimer's amyloid, such as Alzheimer's disease. Also provided are methods of treating or reducing the risk of developing β-amyloid production, β-amyloid deposition, β-amyloid neurotoxicity (including abnormal hyperphosphorylation of tau) and microgliosis associated with cerebral accumulation of Alzheimer's amyloid by administering therapeutically effective amounts of compounds which in combination can decrease β-amyloid production and capacitative calcium entry in cells. Further provided are methods for diagnosing diseases associated with cerebral accumulation of Alzheimer's amyloid in animals or humans by administering diagnostically effective amounts of the compounds.
Owner:ARCHER PHARMA +1
Leptin compositions and methods for treating progressive cognitive function disorders resulting from accumulation of neurofibrillary tangles and amlyoid beta
ActiveUS20100113358A1Reducing and preventing progressionDecrease Aβ productionOrganic active ingredientsNervous disorderNeurofibrillary tangleCognitive diseases
The present disclosure provides compositions containing a leptin product and methods of clinical therapy and diagnostic methods for progressive cognitive disorders. According to one aspect, the described invention provides a method for treating a progressive cognitive disorder. According to another aspect, the described invention provides a method for improving resilience of cognitive function in a subject in need thereof. According to another aspect, the described invention provides a method for identifying an effective therapeutic agent for treating a progressive cognitive dysfunction disease or disorder that results from at least one of accumulation of Aβ, hyperphosphorylation of tau, or accumulation of neurofibrillary tangles.
Owner:NEUROTEZ
Pharmaceutical Compositions for the Treatment of Neurodegenerative Disorders
InactiveUS20080206356A1Low priceImprove solubilityBiocideHeavy metal active ingredientsTherapeutic treatmentInsulin resistance
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.
Owner:UNIV DE BARCELONA +1
Antibodies specific for hyperphosphorylated tau and methods of use thereof
Owner:H LUNDBECK AS
Treatment of tauopathies by passive immunization targeting the n-terminal projection domain of tau
ActiveUS20160102138A1Reducing tau levelDecreased tau hyperphosphorylatedImmunoglobulins against animals/humansAntibody ingredientsPassive ImmunizationsTau hyperphosphorylation
A method of treating tau pathologies, such as Alzheimer's disease, involving the administration of antibodies specific to the amino terminal region of human tau (amino acid residues 6-18 or 184-195) to provide passive immunization. The administration of such antibodies can reduce total tau levels, decrease tau hyperphosphorylation, and improve reference memory. Passive immunization with antibodies targeting the N-terminal projection domain of tau reduces both total and hyperphosphorylated tau was found effective in aged 3×Tg-AD mice, a generally accepted mouse model of Alzheimer's disease and frontotemporal dementia in humans.
Owner:RES FOUDATION FOR MENTAL HYGIENE INC
Multisite phosphorylated peptide (protein) recognizing compound and detection method, imaging method, alzheimer's disease diagnosing method and reagent kit using the same
ActiveUS20090233373A1High sensitivityNervous disorderNickel organic compoundsPhosphatePhosphoric acid
There are provided a novel compound which captures a multisite phosphorylated peptide or protein specifically to a phosphorylation site and a method for detecting a multisite phosphorylated peptide or protein using the same. In particular, there are provided a compound which specifically detects an excessively phosphorylated tau protein observed in the brain affected by Alzheimer's disease and a method for diagnosing Alzheimer's disease in vitro or in vivo using the compound. By bringing a metal complex compound having two dipicolylamine (Dpa) moieties and a spacer including a chromogenic or luminescent functional group or atom group into contact with a multisite phosphorylated peptide or protein, the compound recognizes the distance between phosphate groups and specifically binds to the peptide or the protein, and a multisite phosphorylated peptide or protein or a kinase activity is optically detected by measuring the change, or a multisite phosphorylated peptide or protein or kinase activity is imaged by an optical imaging method applying the change in the luminescence.
Owner:CANON KK
Application of Li2WO4 in preparing medicine
InactiveCN101036669AInhibitory activityInhibit hyperphosphorylationNervous disorderInorganic active ingredientsCortical neuronsProtein C
The invention discloses an application of tungstate lithium for preparing a medicine, in particular an application for preparing drug for treating neurodegenerative disease, neuropathy caused by diabetes, and cerebral ischemia including cerebral dysfunction. Both of activity of anion and cation of the tungstate lithium can perform synergistic reaction to inhibit activity of a GSK-3 much better. By inhibiting activity of a GSK-3 alpha, generation of the A beta is reduced to decrease SP; by inhibiting activity of a GSK-3 beta, hyperphosphorylation of tau protein is inhibitted to reduce NFT. Thereby, survival and wound repair of neurocyte are promoted even in a state of ischemia and anoxia to improve learning and memory dysfunction by increasing content of BDNF in cortical neurons.
Owner:JINAN UNIVERSITY
Application of acteoside in preparing medicine for treating alzheimer disease
InactiveCN102755341AAdjustment levelInhibition formationOrganic active ingredientsNervous disorderNervous systemCholesterol
The invention relates to an application of acteoside in preparing a medicine for treating alzheimer disease. The acteoside is used for preventing the alzheimer disease by multi-target-point action. The acteoside is synthesized artificially or is obtained from plants. Verified by in vivo and vitro experiments, the acteoside has the advantages that the central cholinergic nervous system can be improved, the level of glutamic acid can be adjusted, the formation and deposition of beta amyloid protein (Abeta) can be inhibited, the action of neuroprotection is achieved, the hyperphosphorylation of tau protein is inhibited, the antioxidant action is achieved, the cerebral circulation is improved, and cholesterol can be reduced, so that the multi-target-point prevention and treatment of the alzheimer disease is realized.
Owner:闫明
Medicament for preventing and treating senile dementia
ActiveCN104479027AEasy Inducible Expression PuritySuitable for intravenous injectionNervous disorderPeptide/protein ingredientsMicrotubule associated protein tauMemory disorder
The invention discloses a small molecular polypeptide TAT-siP-PTPN1-HA and application thereof in preparation of a medicament for treating or preventing senile dementia. An artificially synthesized TAT protein transduction structural domain and an siP-PTPN1-HA fusion protein polypeptide TAT-siP-PTPN1-HA are used, TAT can carry the siP-PTPN1-HA protein polypeptide to pass through a blood-brain carrier via blood to be absorbed by neurons, and by applying the small molecular polypeptide TAT-siP-PTPN1-HA to an in-vivo senile dementia model, the biological action of blocking the binding of miR-124 and protein tyrosine phosphatase, non-receptor type 1, PTPN1 3'-non-coding sequence (3'-untranslated region, 3'-UTR) can be effectively realized, the expression of PTPN1 is further effectively reversed, excessive phosphorylation of microtube-associated protein tau and amyloid protein deposition, as well as animal learning and memory disorders represented by an senile dementia model animal are improved, and a new direction is provided for further development of the medicaments for clinical treatment of senile dementia.
Owner:HUAZHONG UNIV OF SCI & TECH
Permeable glycosidase inhibitors and uses thereof
ActiveUS20150152127A1Isotope introduction to sugar derivativesBiocideN acetylglucosaminidaseGlycosidase inhibitor
The present invention is directed to compounds and pharmaceutical formulations comprising these compounds which are useful as O-linked N-acetylglucosaminidase (O-GlcNAcase) inhibitors, and thus may be useful for the treatment of certain disorders such as Alzheimer's disease including reducing NFTs and / or hyperphosphorylated tau. The invention is also directed to use of the compounds as O-GlcNAcase imaging agents.
Owner:ALECTOS THERAPEUTICS
Antibodies specific for hyperphosphorlated tau for the treatment of ocular diseases
ActiveUS10995137B2Reduce accumulationNervous disorderPeptide/protein ingredientsRetinoidMacula lutea degeneration
The present invention is based on antibodies which are both highly specific for hyperphosphorylated pathogenic P-S396 tau and highly specific for labelled sections of the human retina, as well as to methods of using these antibodies and their tau binding fragments in the treatment of retinoid amyloidosis, age related macular degeneration (ARMD), and glaucoma.
Owner:H LUNDBECK AS
Tacrine-phenothiazine isodiad compound and preparation method thereof
ActiveCN102936244ALow toxicityImprove bindingNervous disorderOrganic chemistryStructural formulaPhenothiazine
The invention discloses a tacrine-phenothiazine isodiad compound and a preparation method thereof, wherein the tacrine-phenothiazine isodiad compound has a structural formula shown by a general formula (I) and a general formula (II): the tacrine-phenothiazine isodiad compound is combined with tacrine and phenothiazine parent nucleuses which are used for effectively treating senile dementia, is added with a proper length of a linking group, has dual inhibition functions of Acetylcholinesterase (AchE) and tau protein hyperphosphorylation, is relatively lower in toxicity, and can be used for prevention and treatment of Alzheimer's Dieses (AD).
Owner:HEFEI UNIV OF TECH
Compounds for inhibiting beta-amyloid production and methods of identifying the compounds
InactiveUS20060188938A1Decrease capacitative calcium entryReduce productionBiocideCompound screeningMicrogliosisS amyloid
Provided are compounds useful for treating diseases associated with a cerebral accumulation of Alzheimer's amyloid, such as Alzheimer's disease. Also provided are methods for screening for such compounds, by measuring capacitative calcium entry in cells which optionally overexpress APP or a fragment thereof. Also provided are methods of treating or reducing the risk of developing β-amyloid production, β-amyloid deposition, β-amyloid neurotoxicity (including abnormal hyperphosphorylation of tau) and microgliosis associated with cerebral accumulation of Alzheimer's amyloid by administering therapeutically effective amounts of compounds which decrease β-amyloid production and capacitative calcium entry in cells. Further provided are methods for diagnosing diseases associated with cerebral accumulation of Alzheimer's amyloid in animals or humans by administering diagnostically effective amounts of compounds which inhibit capacitative calcium entry in cells.
Owner:ARCHER PHARMA +1
Compounds for inhibiting beta-amyloid production and methods of identifying the compounds
InactiveUS20070037855A1Decrease capacitative calcium entryReduce productionBiocideCompound screeningMedicineMicrogliosis
Provided are compounds useful for treating diseases associated with a cerebral accumulation of Alzheimer's amyloid, such as Alzheimer's disease. Also provided are methods for screening for such compounds, by measuring capacitative calcium entry in cells which optionally overexpress APP or a fragment thereof. Also provided are methods of treating or reducing the risk of developing β-amyloid production, β-amyloid deposition, β-amyloid neurotoxicity (including abnormal hyperphosphorylation of tau) and microgliosis associated with cerebral accumulation of Alzheimer's amyloid by administering therapeutically effective amounts of compounds which decrease β-amyloid production and capacitative calcium entry in cells. Further provided are methods for diagnosing diseases associated with cerebral accumulation of Alzheimer's amyloid in animals or humans by administering diagnostically effective amounts of compounds which inhibit capacitative calcium entry in cells.
Owner:ALZHEIMERS INST OF AMERICA
Medicinal composition for treating Alzheimer's disease and preparation method and application of medicinal composition
InactiveCN106692551AInhibit hyperphosphorylationImprove expression levelNervous disorderConiferophyta medical ingredientsSenile dementiaProtein C
The invention provides a medicinal composition for treating the Alzheimer's disease and a preparation method and application of the medicinal composition. Specifically, the invention provides the medicinal composition which is prepared from the following traditional Chinese medicines: ginseng, poria cocos, rehmannia, dogwood, polygala tenuifolia, rhizoma acori graminei, jujube kernels and platycladi seeds. The invention further provides a preparation method and application of the medicinal composition. The medicinal composition is capable of remarkably inhibiting over phosphorylation of downstream tau protein and increasing the expression level of CaMKII, and has long-term effectiveness and security in treatment on senile dementia, particularly the Alzheimer's disease.
Owner:田金洲 +1
Human fg01 gene and its applications
InactiveUS20100286252A1Stimulating cAMP productionInhibit phosphorylationOrganic active ingredientsSugar derivativesScreening methodBiology
A human gene, fg01, on chromosome 8, is identified, as well as a truncated form on chromosome 5. Upregulation appears to suppress the Alzheimer's phenotype, (AB plaques and hyperphosphorylated tau tangles) which may address the onset of symptoms or progression of symptoms associated with AD. Screening methods are also set forth.
Owner:FUNCTIONAL GENETICS
Multisite phosphorylated peptide (protein) recognizing compound and detection method, imaging method, alzheimer's disease diagnosing method and reagent kit using the same
A compound which captures a multisite phosphorylated peptide or protein specifically to a phosphorylation site and a method for detecting the peptide or protein using the compound. Particularly, a compound which specifically detects an excessively phosphorylated tau protein observed in the brain affected by Alzheimer's disease and a method for diagnosing Alzheimer's disease in vitro or in vivo using the compound are provided. By bringing a metal complex compound having two dipicolylamine (Dpa) moieties and a spacer including a chromogenic or luminescent functional or atom group into contact with a multisite phosphorylated peptide or protein, the compound recognizes the distance between phosphate groups and specifically binds to the peptide or protein, and a multisite phosphorylated peptide or protein or kinase activity is optically detected by measuring the change, or a multisite phosphorylated peptide or protein or kinase activity is imaged by an optical imaging method applying the change in luminescence.
Owner:CANON KK
Alzheimer's diagnosis
ActiveUS20110136254A1Easy to diagnoseBiological material analysisBiological testingDiseasePhosphorylation
Evaluation of VLP-I levels in combination with at least one of amyloid-β peptide (AB), hyperphosphorylated tau (pTau) or total tau (tTau) levels in samples of biological fluid improves the accuracy of diagnosis of Alzheimer's disease.
Owner:WASHINGTON UNIV IN SAINT LOUIS
Tau resisting antibody and application thereof to treating Alzheimer disease and traumatic brain injury
ActiveCN110028583AImprove symptoms of neurodegenerative diseasesSymptoms improvedNervous disorderImmunoglobulins against animals/humansAlzheimer's diseaseTraumatic brain injury
The invention aims to provide a Tau resisting antibody and an application thereof to treating Alzheimer disease and traumatic brain injury. The antibody can be in specific binding with tau protein, and particularly can be in specific binding with tau protein in excessive phosphorylation. The antibody is given, the expression of tau protein in abnormal phosphorylation in an Alzheimer disease mousemodel can be delayed, and the effect of preventing or treating neurodegenerative diseases related to tau protein, includingthe Alzheimer disease, the traumatic brain injury and the like can be achieved.
Owner:WENZHOU MEDICAL UNIV
Benzazocine-ring compound inhibition of tau hyperphosphorylation
InactiveUS20140094482A1Inhibition formationReduce the impactBiocideNervous system cellsPharmacophoreEnantiomer
A method of inhibiting hyperphosphorylation 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 a FLNA-binding effective amount of a FLNA-binding benzazocine-ring compound or a pharmaceutically acceptable salt thereof such as a) an opioid receptor antagonist compound or b) a mixed opioid receptor agonist and antagonist (agonist / antagonist) compound, c) an opioid receptor agonist compound or d) an enantiomer of an opioid receptor interacting compound, that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1. The administered compound preferably contains at least four of the six pharmacophores of FIGS. 5-10.
Owner:PAIN THERAPEUTICS INC
Protein associated with cell stress response
InactiveUS7186530B1Sugar derivativesMicrobiological testing/measurementHuman brain tumorPhosphorylation
A stress-phosphorylated endoplasmic reticulum protein, Nogo B, is provided. The protein is hyperphosphorylated as a result of exposure of cells to stress. Two transcripts of Nogo B are identified in human tissues, and the longer transcript is predominant in human brain tumor samples.
Owner:CHIRON CORP
Use of itolizumab to reduce phosphorylation of cd6
InactiveUS20190248913A1Decrease ALCAM-CDReducing CD hyper phosphorylationAntipyreticAnalgesicsMechanism of actionActivation cells
The present invention discloses a key mechanism of action of Itolizumab that involves a decrease in an activating ALCAM-CD6 co stimulatory signal by directly reducing CD6 hyperphosphorylation and preventing the docking of key molecules associated with T cell activation and signaling.
Owner:BIOCON LTD
Application of miRNA 200 cluster as marker for diagnosing and/or treating Alzheimer's disease
InactiveCN111269977AReduce accumulationPromote apoptosisNervous disorderMicrobiological testing/measurementSerum samplesMedicine
The invention discloses an application of miRNA 200 cluster as a marker for diagnosing and / or treating Alzheimer's disease. The invention provides application of miRNA 200 cluster micro RNA in diagnosis and treatment of Alzheimer's disease. AD model cells, AD model animals, naturally aged animals and clinical serum samples are used; the expression quantity of the miRNA 200 cluster in a human bodyis detected by using a primer aiming at the miRNA 200 cluster micro RNA marker; it is found that the expression of miRNA 200-cluster micro RNA in the Alzheimer's disease process is significantly reduced; Abeta generation, tau protein excessive phosphorylation and apoptosis-like degeneration in AD lesion are changed by targeting BACE1 and PRKACB, so that miRNA 200 cluster micro RNA can be used as anew Alzheimer's disease marker for auxiliary diagnosis and treatment of Alzheimer's disease.
Owner:MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
Composition and Method for the Treatment of Tauopathies
InactiveUS20070232584A1High degreeConvenient synthetic accessBiocideNervous disorderDepressantTau hyperphosphorylation
The present invention refers to the use of a specific indolocarbazole compound of general formula (1) or a pharmaceutically-acceptable a salt thereof for the preparation of a pharmaceutical composition for the prevention or treatment of a neurode-generative and / or dementing illness driven by the molecular pathology of microtubule-associate tau such as Alzheimer's disease, frontal lobe dementia, Pick's disease, Parkinson disease with dementia, corticobasal degeneration, argyrophilic grains disease, or supranuclear palsy. A method for treating or preventing such illnesses is also disclosed. Furthermore, methods for the identification of efficacious inhibitors of neurofibrillary degeneration, and methods for the determination of an appropriate dosage of an inhibitor of the PHF-type tau hyperphosphorylation for the treatment of a condition characterized by neurofibrillary pathology are described.
Owner:TAU PHARM LLC
Pyridine derivative and preparation method and application thereof
InactiveCN112010846AOrganic chemistryGeneral/multifunctional contrast agentsNeurogeniaNeurofibrillary tangle
The invention relates to a pyridine derivative and a preparation method and application thereof. Specifically, the invention provides a compound shown as a formula I, or a pharmaceutically acceptablesalt, or a hydrate, or a solvate, or a conformational isomer, or a crystal form, or an isotope replacement form thereof, and a preparation method and application thereof. Experimental results show that the pyridine compound is labeled by radionuclide and can be used as a Tau protein tracer agent for identifying neurofibrillar entanglement (NFTs) formed by abnormal aggregation of over-phosphorylated Tau protein in the brain, and can be used for diagnosing neurofibrillar entanglement related diseases, can also be used for monitoring the progress of the diseases in the treatment process, provideshigher and more accurate diagnosis and tracking for patients with the neurofibrillar entanglement related diseases or potential patients, and has a good application prospect in clinical diagnosis.
Owner:WEST CHINA HOSPITAL SICHUAN UNIV
Transgenic animals expressing transglutaminase II
InactiveUS20060015959A1Inhibit and prevent cross-linkingRapid and economical and suitableAnimal cellsImmunoglobulin superfamilyAmygdalaThalamus
The invention provides transgenic, non-human animals and transgenic non-human mammalian cells harboring a transgene encoding a TGII (activator of the protein kinase cdk 5) polypeptide. The two neuropathological lesions associated with Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles (NFTs), composed predominantly of amyloid β peptides and hyperphosphorylated tau, respectively. While animal models for plaque formation exist, there is no animal model that recapitulates the formation of NFTs. This invention provides transgenic mice that overexpress human TGII, an activator of cdk5, resulting in tau that is hyperphosphorylated at AD-relevant epitopes. Deposition of tau is detected in the amygdala, thalamus and cortex. Increased phosphorylated neurofilament, silver-positive neurons and neuronal death are also observed in these regions. We conclude that the overexpression of TGII, an activator of cdk5, is sufficient to produce hyperphosphorylation of tau and neuronal death. The TGII transgenic mouse represents the first model for tau pathology in AD.
Owner:WARNER-LAMBERT CO
Compounds for Inhibiting Beta-Amyloid Production
InactiveUS20090017112A1Reduce productionBiocideNervous disorderAlzheimer's Disease Amyloid ProteinMicrogliosis
Provided are compounds useful for treating diseases associated with a cerebral accumulation of Alzheimer's amyloid, such as Alzheimer's disease. Also provided are methods of treating or reducing the risk of developing β-amyloid production, β-amyloid deposition, β-amyloid neurotoxicity (including abnormal hyperphosphorylation of tau) and microgliosis associated with cerebral accumulation of Alzheimer's amyloid by administering therapeutically effective amounts of the compounds. Further provided are methods for diagnosing diseases associated with cerebral accumulation of Alzheimer's amyloid in animals or humans by administering diagnostically effective amounts of the compounds.
Owner:ALZHEIMERS INST OF AMERICA
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