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33 results about "Presenilin" patented technology
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Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease complex. They were first identified in screens for mutations causing early onset forms of familial Alzheimer's disease by Peter St George-Hyslop at the Centre for Research in Neurodegenerative Diseases at the University of Toronto, and now also at the University of Cambridge. Vertebrates have two presenilin genes, called PSEN1 (located on chromosome 14 in humans) that encodes presenilin 1 (PS-1) and PSEN2 (on chromosome 1 in humans) that codes for presenilin 2 (PS-2). Both genes show conservation between species, with little difference between rat and human presenilins. The nematode worm C. elegans has two genes that resemble the presenilins and appear to be functionally similar, sel-12 and hop-1.
Methods for correcting presenilin point mutations
Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a nucleic acid encoding a mutant Presenilin1 protein to correct a point mutation associated with a disease or disorder, e.g., with familial Alzheimer's disease. The methods provided are useful for correcting a PSEN1 point mutation within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing enzymes or enzyme domains, e.g., deaminase domains, are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing enzymes or domains, are provided.
Owner:PRESIDENT & FELLOWS OF HARVARD COLLEGE
Nucleic acid participating in the formation of presenilin-2-gene exon 5-defective splicing variant
InactiveUS20040267004A1Avoid it happening againExpected treatment and/or prevention of a diseaseCompound screeningOrganic active ingredientsMedicineNeuro-degenerative disease
The present invention provides a means for treatment and / or prevention of a disease caused by aberrant splicing, a neurodegenerative disease represented by Alzheimer's disease, or the like. The present invention relates to a nucleic acid which can be associated with generation of a splice variant that lacks exon 5 of presenilin-2 gene, an inhibitor for inhibiting a binding between protein-nucleic acid caused by aberrant splicing, and a method for screening the inhibitor.
Owner:JAPAN SCI & TECH CORP
Alarm related peptides and nucleic acids and diagnosis using them
We have identified a novel protein, named ALARM or delta-catenin, on the basis of its ability to bind to presenilin 1. ALARM contains 4 copies of the arm repeat and is expressed almost exclusively in brain tissue.
Owner:THE BRIGHAM & WOMEN S HOSPITAL INC
Phosphoinositide modulation for the treatment of alzheimer's disease
InactiveUS20080312187A1Enhance memoryInhibited synaptic dysfunctionBiocideNervous disorderPhosphoric acidPhosphatidylinositol
The present invention relates to methods of treating Alzheimer's Disease which utilize agents that increase neuronal phosphotidylinositol 4,5-biphosphate (PIP2), and to differentiated stem cell-based assay systems that may be used to identify agents that modulate phosphoinositide levels and thereby treat a variety of diseases. It is based, at least in part, on the discovery that edelfosine, an agent that increases PIP2 levels by inhibiting an enzyme that catalyzes PIP2 breakdown, decreases levels of neurotoxic A&bgr;42 peptide, particularly in cells expressing a mutant presenilin gene associated with Familial Alzheimer's Disease.
Owner:THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
Knockin gene-mutated mouse comprising a mutant presenilin-1 gene
A gene-mutated animal such as a mouse which comprises a mutant prsenilin-1 gene comprising a DNA having a sequence encoding a mutant presenilin-1 protein in which an amino acid is substituted with a different amino acid in an amino acid sequence of a presenilin-1 protein; for example, a mutant presenilin protein in which isoleucine at position 213 is substituted with an amino acid other than isoleucine, e.g., threonine, in a mouse presenilin-1 protein. The animal is useful as an animal model which has pathological conditions closer to a human patient with Alzheimer's disease.
Owner:DAIICHI PHARMA CO LTD
Modulator of gamma-secretase
InactiveUS20070287666A1Inhibit productionQuick effectCompound screeningNervous disorderGamma secretasePresenilin
The invention relates to modulators of γ-secretase and to methods and uses related thereto. In one embodiment the modulators do not modulate ε-secretase activity. In another embodiment the invention relates to presenilin complex component. In one embodiment the presenilin component is TMP21.
Owner:FRASER PAUL E +3
Methods and compositions for treating neurodegenerative disorders and alzheimer's disease and improving normal memory
InactiveCN101454671AFunction increaseCell receptors/surface-antigens/surface-determinantsBiological testingMedicineDisease cause
The disclosure relates generally to neurodegenerative disorders and more specifically to a group of presenilin / G-protein / c-src binding polypeptides and methods of use for modulating signaling and progression of Alzheimer's disease.
Owner:RGT UNIV OF CALIFORNIA
Functional screening
Screening methods for identifying molecules that interact with and / or regulate accumulation and stabilization of unstable proteins are provided. The screening methods involve generation of chimeric proteins comprising a region of an unstable protein linked to a region of a marker gene product. Changes in the levels of the unstable protein, due to accumulation, and / or stabilization and / or hyperaccumulation are then determined by analyzing the change in the marker gene product level. The marker gene product can be an antibiotic resistance gene that confers antibiotic resistance by stoichiometrically binding to the antibiotic or it can be a fluorescent protein region. Thus, antibiotic resistance screening or fluorescence imaging or cell sorting methods can be used to detect changes in the levels of the unstable chimeric proteins. Unstable proteins suitable for this screening method include, but are not limited to, membrane proteins such as ion channels, receptors, or presenilins.
Owner:CHICAGO UNIV OF THE
Preparation method of composite animal model with Alzheimer disease
InactiveCN102058619AWith typical morphological changesDecreased learning and memory abilityAluminium/calcium/magnesium active ingredientsIntraperitoneal routeContamination
The invention relates to a preparation method of composite animal model with the Alzheimer disease. A healthy male APP (amyloid protein precursor) / PS1 (presenilin) double transgenic mouse is chosen, and a 1mol / LAlcl3.6H2O solution is used for intraperitoneal injection contamination for 30 times, and 0.05mL of the solution is injected once. After being detected by the neuroethology and the morphology, the composite animal model with the Alzheimer disease, which is obtained by the method, has obviously lowered learning and memory capability compared with animals in a control group and has the typical morphologic features, such as age pigments, neurofibril tangle, amyloid protein deposition, granulovacuolar degeneration and the like, can better simulate the neurobehavioral reaction of the Alzheimer disease and has all typical morphological changes of the Alzheimer disease. The composite animal model with the Alzheimer disease can be used for screening medicaments and researching the mechanism of the Alzheimer disease.
Owner:SHANXI MEDICAL UNIV
G Protein-Coupled Receptor Antagonist and Its Use for Preventing and Treating Alzheimer's Disease
A method for screening a reagent for treating or preventing Alzheimer's disease or related neurological pathology includes the steps of: (a) activating a receptor and determining a first extent of endocytosis of the receptor, wherein the receptor is a G-protein coupled receptor that associates with presenilin-1; (b) activating the receptor under the same conditions as in step (a), in the presence of a candidate reagent, and determining a second extent of endocytosis of the receptor; (c) determining a difference between the first extent of endocytosis and the second extent of endocytosis; and (d) repeating steps (a)-(c), if the difference is less than a threshold. Uses of receptor antagonists for manufacturing medicaments for treating or preventing Alzheimer's disease or related neurological pathology, wherein the receptor antagonists inhibit endocytosis of a G-protein coupled receptor that associates with presenilin-1 during endocytosis.
Owner:SHANGHAI EW MEDICINE CO LTD
Proteins related to schizophrenia and uses thereof
Presenilin Associated Membrane Protein (PAMP), and nucleic acids encoding this protein, are provided. PAMP and PAMP nucleic acids provide diagnostic and therapeutic tools for evaluating and treating or preventing neurodevelopmental and neuropsychiatric disorders. In a specific embodiment, mutations in PAMP are diagnostic for schizophrenia. The invention further relates to screening, particularly using high-throughput screens and transgenic animal models, for compounds that modulate the activity of PAMP and presenilins. Such compounds, or gene therapy with PAMP, can be used in treating neurodevelopmental and neuropsychiatric disorders, particularly schizophrenia. In addition, the invention provides PAMP mutants, nucleic acids encoding for PAMP mutants, and transgenic animals expressing PAMP mutants, which in a preferred aspect result in biochemical, morphological, or neuropsychological changes similar to those associated with schizophrenia.
Owner:THE GOVERNINIG COUNCIL OF THE UNIV OF TORANTO
Presenilin enhancers assays
The invention provides methods and compositions relating to pen polypeptides having pen-specific structure and activity, related polynucleotides and modulators of pen function. The invention provides isolated pen hybridization probes and primers capable of specifically hybridizing with natural pen genes, pen-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis (e.g. genetic hybridization screens for pen transcripts), therapy (e.g. pen inhibitors to modulate APP processing) and in the biopharmaceutical industry (e.g. as immunogens, reagents for screening chemical libraries for lead pharmacological agents, etc.).
Owner:EXELIXIS PHARMA
G protein-coupled receptor antagonist and its use for preventing and treating alzheimer's disease
The invention discloses methods for screening a reagent for treating or preventing Alzheimer's disease or related neurological pathology. A method according to the invention includes the steps of: (a) activating a receptor and determining a first extent of endocytosis of the receptor, wherein the receptor is a G-protein coupled receptor that associates with presenilin-1; (b) activating the receptor under the same conditions as in step (a), in the presence of a candidate reagent, and determining a second extent of endocytosis of the receptor; (c) determining a difference between the first extent of endocytosis and the second extent of endocytosis; and (d) repeating steps (a)-(c), if the difference is less than a threshold. The invention also disclose uses of receptor antagonists for manufacturing medicaments for treating or preventing Alzheimer's disease or related neurological pathology, wherein the receptor antagonists inhibit endocytosis of a G-protein coupled receptor that associates with presenilin-1 during endocytosis.
Owner:SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
Presenilin associated membrane protein (PAMP)and uses thereof
InactiveUS7439326B2Stimulates PAMP activityAnimal cellsCell receptors/surface-antigens/surface-determinantsMutantCell Membrane Proteins
Presenilin Associated Membrane Protein (PAMP), and nucleic acids encoding this protein, are provided. PAMP and PAMP nucleic acids provide diagnostic and therapeutic tools for evaluating and treating or preventing neurodegenerative diseases. In a specific embodiment, mutations in PAMP are diagnostic for Alzheimer's Disease or spina bifida. The invention further relates to screening, particularly using high-throughput screens and transgenic animal models, for compounds that modulate the activity of PAMP and presenilins. Such compounds, or gene therapy with PAMP, can be used in treating neurodegenerative diseases, particularly Alzheimer's Disease. In addition, the invention provides PAMP mutants, nucleic acids encoding for PAMP mutants, and transgenic animals expressing PAMP mutants, which in a preferred aspect result in biochemical changes similar to those induced by mutations in βAPP, PS1, or PS2, associated with familial Alzheimer's disease.
Owner:THE GOVERNINIG COUNCIL OF THE UNIV OF TORANTO
Medicinal compositions
InactiveUS20050065102A1Suppressing neuronal deathGood introductionOrganic active ingredientsNervous disorderDiseaseExon
To provide a means useful for treating or preventing a disease such as a brain disorder or a neurodegenerative disease even more efficiently and even more sustainedly. The present invention relates to an inhibitor capable of inhibiting a binding between HMG-I protein and exon 5 of presenilin-2 mRNA, an agent for suppressing neuronal death, capable of suppressing neuronal death, a pharmaceutical composition which is useful for treatment or prevention of a disease caused by the generation of a splice variant that lacks exon 5 of presenilin-2 mRNA, a method for treating or preventing the disease and a use of the inhibitor.
Owner:JAPAN SCI & TECH CORP +1
Method of treating alzheimer's disease using pharmacological chaperones to increase presenilin function and gamma-secretase activity
InactiveUS20130102538A1High activityFunction increaseBiocideNervous disorderDiseasePharmacological chaperone
Owner:AMICUS THERAPEUTICS INC
Application of pearl extract in preparation of medicine, health care product and cosmetic capable of inhibiting generation of presenilin
ActiveCN106890314AInhibits the ability to synthesize progerinCosmetic preparationsPeptide/protein ingredientsFibroblastFibre cell
The invention relates to an application of a pearl extract. According to the application, multiple extracting modes are utilized for obtaining a pearl active ingredient, experimental results show that the pearl extract has obvious capability of inhibiting fibroblasts from synthesizing presenilin, and presenilin content is reduced by about 4% compared to control. Extraction of the pearl extract and discovery of inhibiting synthesis of the presenilin provide one effective and valid active addition agent for medicines, cosmetics and health food.
Owner:OSMUN BIOLOGICAL
Expression cassette and vector comprising alzheimer's disease-related mutant genes and cell line transformed by means of same
The present invention relates to expression cassette and vector comprising Alzheimer's disease-related genes and a cell line transformed by means of same, and more specifically, the expression cassette according to the present invention comprises amyloid precursor protein (APP), Tau protein, and presenilin-1 (PS1) genes associated with Alzheimer's disease so that mutant genes thereof can be simultaneously expressed. Additionally, the present invention relates to a cell line transformed by means of the expression cassette or vector comprising said genes, and further, to an animal model transformed by means of the vector or cell line.
Owner:MIRAE BIOTECH CO LTD
Medicine composition for preventing and controlling AD (Alzheimer Disease)
InactiveCN108210507AAvoid problemsImprove spatial learning and memoryOrganic active ingredientsNervous disorderRutinBiology
The invention discloses a medicine composition for preventing and controlling AD (Alzheimer Disease), and belongs to the field of medicines. The medicine composition has the advantages that the watermaze experiment is performed by an APP / PS1 (amyloid precursor protein / presenilin 1) transgenic mouse (chronic AD model) and a 5XFAD transgenic mouse (acute AD model), and the function of the compoundshown in formula II for improving the space learning and memory abilities of the two mouse is verified; the obvious preventing and treatment function of rutin or derivative of rutin on AD is realized.
Owner:ACADEMY OF MILITARY MEDICAL SCI
Methods for identifying inhibitors of neuronal degeneration
InactiveUS6979537B2Inhibiting neuronal degenerationInhibitory activityMicrobiological testing/measurementTissue cultureNeuronal degenerationNf κb activation
The present invention concerns methods and means for identifying inhibitors of neuronal degeneration, and their use in the treatment of neurodegenerative disorders. In particular the invention concerns methods and means for identifying inhibitors of neuronal degeneration or cell death by taking advantage of the involvement of presenilin (PS) and Par-4 in NF-κB activation.
Owner:SCIOS
Screening G protein-coupled receptor antagonists for methods of treating Alzheimer's disease
InactiveUS8026073B2Compound screeningNervous disorderG protein-coupled receptorNK1 receptor antagonist
Owner:SHANGHAI EW MEDICINE CO LTD
Proteins related to schizophrenia and uses thereof
Owner:ST GEORGE HYSLOP PETER +1
Components of the presenilin-complex
InactiveUS20080176803A1Improve reliabilityNervous disorderPeptide/protein ingredientsSoftware engineeringMechanical engineering
Owner:CELLZOME LTD
Binding domains between presenilins and their substrates as targets for drug screening
InactiveUS7198903B2Inhibition formationContributes to long-term potentiationHydrolasesPeptide/protein ingredientsMolecular bindingTELENCEPHALIN
The present invention relates to the identification of the molecular binding domains between presenilins and its substrates such as amyloid precursor protein and telencephalin. These binding domains can be efficiently used in drug screening assays to screen for compounds capable of modulating the interaction between presenilins and type I transmembrane proteins. The invention further relates to compounds capable of modulating the interaction.
Owner:VLAAMS INTERUNIVERSITAIR INST VOOR BIOTECHNOLOGIE VZW
Expression cassette and vector comprising Alzheimer's disease-related mutant genes and cell line transformed by means of same
The present invention relates to expression cassettes and vectors comprising Alzheimer's disease-related genes and a cell line transformed by the disclosed expression cassettes and vectors, and more specifically, the expression cassettes according to the present invention comprise amyloid precursor protein (APP), Tau protein, and presenilin-1 (PS1) genes associated with Alzheimer's disease so that mutant genes thereof can be simultaneously expressed. Additionally, the present invention relates to a cell line transformed by the disclosed expression cassettes or vectors comprising APP, Tau protein, and PS1 genes, and further, to an animal model transformed by the vectors or cell line.
Owner:MIRAE BIOTECH CO LTD
Identifying agents to treat alzheimer's disease-related decreased sorting behavior by administration to a triple transgenic mouse expressing mutant forms of APP, presenilin or tau
The method of the invention is useful for evaluating pharmaceutical compositions for treatment of neurological diseases encompassing neurological or neurodegenerative diseases associated with cognitive dysfunction and, in particular, dementia; schizophrenia; anxiety; depression; and pain using a rodent behavioral assay, wherein the method is useful in testing compositions useful in the modulation, amelioration, prevention, or treatment of dementia using a non-human animal carrying at least a transgene for human amyloid-beta protein or human tau and transgenes causing the elevated production of the human amyloid-beta protein in the animal as compared to nontransgenic animals of the same genetic background and the behavior is a nesting behavior.
Owner:JANSSEN BIOTECH INC
Nucleic acid related to Alzheimer's disease and application of nucleic acid
The invention discloses a nucleic acid related to Alzheimer's diseases and the application of the nucleic acid. The nucleic acid related to Alzheimer's diseases is formed by generating c.505C>A mutation in an encoding zone of a wild PSEN2 (Presenilin) gene. The nucleic acid disclosed by the invention is a novel related pathogenic nucleic acid related to Alzheimer's diseases, discovery of the nucleic acid or a pathogenic mutation site further expands and completes detection and research on Alzheimer's diseases, a novel detection site and novel detection methods and ways are provided for diagnosis or treatment on the diseases, and a novel target site is also provided for development of target medicines.
Owner:SHENZHEN HUADA GENE INST
Preferential Inhibition of Presenilin-1
The invention provides methods for determining whether an agent preferentially inhibits Presenilin-1-comprised γ-secretase relative to Presenilin-2-comprised γ-secretase. The invention also provides agents that preferentially inhibit Presenilin-1-comprised γ-secretase relative to Presenilin-2-comprised γ-secretase, pharmaceutical compositions comprising such compounds, and methods of treating Alzheimer's disease using such compounds. The invention also discloses that the N-terminal domain of presenilin-1 and -2 determines the difference in the production of Aβ by PS1-comprised and PS2-comprised gamma secretases. This finding identified the structural determinant for the observed difference in the production of Aβ by PS1-comprised and PS2-comprised gamma secretases. Such structural determinant was not identified before. This invention also provides a method for determining whether an agent specifically binds the N terminus of PS1. The invention further provides for methods of treatment of Alzheimer's Disease by administration of an effective dose of an agent which specifically binds PS1, thereby inhibiting PS1 activity.
Owner:ELAN PHARM INC
Novel presenilin associated membrane protein (PAMP) and uses thereof
InactiveUS20110212459A1Cell receptors/surface-antigens/surface-determinantsBacteriaMutantSpina bifida
Presenilin Associated Membrane Protein (PAMP), and nucleic acids encoding this protein, are provided. PAMP and PAMP nucleic acids provide diagnostic and therapeutic tools for evaluating and treating or preventing neurodegenerative diseases. In a specific embodiment, mutations in PAMP are diagnostic for Alzheimer's Disease or spina bifida. The invention further relates to screening, particularly using high-throughput screens and transgenic animal models, for compounds that modulate the activity of PAMP and presenilins. Such compounds, or gene therapy with PAMP, can be used in treating neurodegenerative diseases, particularly Alzheimer's Disease. In addition, the invention provides PAMP mutants, nucleic acids encoding for PAMP mutants, and transgenic animals expressing PAMP mutants, which in a preferred aspect result in biochemical changes similar to those induced by mutations in KNAPP, PS1, or PS2, associated with familial Alzheimer's disease.
Owner:THE GOVERNING COUNCIL OF THE UNIV OF TORONTO
Gene therapy for alzheimer's disease
PendingCN114144425ANervous disorderCell receptors/surface-antigens/surface-determinantsPick's diseaseNeuro-degenerative disease
The present disclosure provides, among other aspects, human codon optimized sequences encoding presenilin 1, as well as methods for using the sequences in gene therapy to treat neurodegenerative diseases, the neurodegenerative diseases include, but are not limited to, Alzheimer's disease, frontotemporal dementia, frontotemporal degeneration, Pick's disease, dementia with Lewy bodies, memory loss, and cognitive impairment including mild cognitive impairment (MCI).
Owner:THE BRIGHAM & WOMEN S HOSPITAL INC +1
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