31 results about "Presenilin" patented technology

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.

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.

The present invention relates to a method for treating an individual having Alzheimer's Disease by using pharmacological chaperones that bind presenelin and thereby increase γ-secretase activity.

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.

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.

The present invention is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description and accompanying figures. Such modifications are intended to fall within the scope of the appended claims.Various publications are cited herein, the disclosures of which are incorporated by reference in their entireties.

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.

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.

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.

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.

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.

The present disclosure provides, among other things, methods for using presenilin based gene therapy to treat neurodegenerative dementia including, but not limited to Alzheimers disease, frontotemporal dementia, frontotemporal lobar degeneration, Picks disease, Lewy body dementia, memory loss, and cognitive impairment including mild cognitive impairment (MCI).