Abstract: The present invention relates to methods for the prevention or treatment of pain by the inhibition of p38 MAP kinase.

Abstract: The present invention is based on the findings that BACE2, a homolog of ?-secretase BACE, is able to stimulate processing of APP in a non-amyloidogenic pathway, thereby suppressing the level of A?. Accordingly, the present invention provides methods and means for the identification and use of modulators of this unique activity of BACE2 to suppress A? production. The compounds identified using the methods and means provided herein may be used as potential candidates for the treatment of Alzheimer's disease and other neurological diseases.

Abstract: The present invention is based on the findings that BACE2, a homolog of ?-secretase BACE, is able to stimulate processing of APP in a non-amyloidogenic pathway, thereby suppressing the level of A?. Accordingly, the present invention provides methods and means for the identification and use of modulators of this unique activity of BACE2 to suppress A? production. The compounds identified using the methods and means provided herein may be used as potential candidates for the treatment of Alzheimer's disease and other neurological diseases by reducing ?-amyloid deposit formation.

Abstract: The present invention provides assays to identify compounds that affect microglial cell activation, and specifically assays to identify compounds that affect secretion of cytokines from these microglial cells by modulating PGE2-mediated activity. The assays of the invention include assays for testing microglial cell activation by contacting microglia with compounds that modulate ?-amyloid PGE2-mediated activation, which can be identified by cellular activity such as secretion of cytokines, e.g., TNF-? and IL-1?,. The effect of the candidate compound can be determined by comparing the effect with a control culture which is not contacted with the compound, or by comparing the effect with a standardized profile.

Abstract: The invention concerns a novel ?-secretase, a method of partially purifying this novel ?-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel ?-secretase has an estimated molecular weight of about 32-39 kDa or 22-26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5-7.0.

Abstract: The invention concerns a novel ?-secretase, a method of partially purifying this novel ?-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel ?-secretase has an estimated molecular weight of about 32-39 kDa or 22-26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5-7.0.

Abstract: The invention concerns a novel ?-secretase, a method of partially purifying this novel ?-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel ?-secretase has an estimated molecular weight of about 32–39 kDa or 22–26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5–7.0.

Abstract: Disclosed herein are methods for identifying inhibitors of neuronal degeneration, and their use in the treatment of neurodegenerative disorders. In particular methods methods are disclosed for identifying inhibitors of neuronal degeneration or cell death by taking advantage of the involvement of presenilin (PS) and Par-4 in NF-?B activation.

Abstract: 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-?B activation.

Abstract: The present invention is based on the findings that BACE2, a homolog of &bgr;-secretase BACE, is able to stimulate processing of APP in a non-amyloidogenic pathway, thereby suppressing the level of A&bgr;. Accordingly, the present invention provides methods and means for the identification and use of modulators of this unique activity of BACE2 to suppress A&bgr; production. The compounds identified using the methods and means provided herein may be used as potential candidates for the treatment of Alzheimer's disease and other neurological diseases.

Abstract: The invention concerns a novel &bgr;-secretase, a method of partially purifying this novel &bgr;-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel &bgr;-secretase has an estmated molecular weight of about 32-39 kDa or 22-26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5-7.0.

Abstract: The present invention relates to methods for the prevention or treatment of pain by the inhibition of p38 MAP kinase.

Abstract: The present invention provides assays to identify compounds that affect microglial cell activation, and specifically assays to identify compounds that affect secretion of cytokines from these microglial cells by modulating PGE2-mediated activity. The assays of the invention include assays for testing microglial cell activation by contacting microglia with compounds that modulate &bgr;-amyloid PGE2-mediated activation, which can be identified by cellular activity such as secretion of cytokines, e.g., TNF-&agr; and IL-1&agr;. The effect of the candidate compound can be determined by comparing the effect with a control culture which is not contacted with the compound, or by comparing the effect with a standardized profile.

Abstract: The present invention is based on the findings that BACE 2, a homolog of &bgr;-secretase BACE, is able to stimulate processing of APP in a non-amyloidogenic pathway, thereby suppressing the level of A&bgr;. Accordingly, the present invention provides methods and means for the identification and use of modulators of this unique activity of BACE 2 to suppress A&bgr; production. The compounds identified using the methods and means provided herein may be used as potential candidates for the treatment of Alzheimer's disease and other neurological diseases.

Abstract: This invention concerns methods and means for the functional cloning of genes encoding proteins or enzymes involved in proteolytic cleavage. The invention is based on the use of caspase expression cassettes comprising the coding sequence of a proteolytic cleavage site flanked by sequences encoding two caspase subunits.

Abstract: The invention relates to the design, construction and use of eukaryotic cell lines useful in the identification of inhibitors of &bgr;-amyloid processing. More specifically, the invention relates to in vitro assays capable of identifying or quantifying a 4.2 kDa &bgr;-amyloid protein. The present invention also provides for DNA and protein molecules for the design, construction and use of eukaryotic cell lines useful in the identification of inhibitors of &bgr;-amyloid processing.

Abstract: 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-&kgr;B activation.

Abstract: The invention relates to the design, construction and use of eukaryotic cell lines useful in the identification of inhibitors of &bgr;-amyloid processing. More specifically, the invention relates to in vitro assays capable of identifying or quantifying a 4.2 kDa &bgr;-amyloid protein. The present invention also provides for DNA and protein molecules for the design, construction and use of eukaryotic cell lines useful in the identification of inhibitors of &bgr;-amyloid processing.

Abstract: The present invention provides assays to identify compounds that affect microglial cell activation, and specifically assays to identify compounds that affect secretion of cytokines from these microglial cells by modulating PGE2-mediated activity. The assays of the invention include assays for testing microglial cell activation by contacting microglia with compounds that modulate &bgr;-amyloid PGE2-mediated activation, which can be identified by cellular activity such as secretion of cytokines, e.g., TNF-&agr; and IL-1&agr;. The effect of the candidate compound can be determined by comparing the effect with a control culture which is not contacted with the compound, or by comparing the effect with a standardized profile.

Abstract: The present invention provides cell-free &ggr;-secretase activity. The method of the invention utilizes a membrane source of APP/&ggr;-secretase mixture in the assay to determine factors that may enhance or decrease enzymatic activity affecting &bgr;-amyloid peptide production. The cell membranes used in the assay may be from cells expressing an endogenous APP or, preferably, cells expressing a recombinant APP. The APP may be full-length or a fragment capable of being proteolytically cleaved by &ggr;-secretase. In addition, the APP expressed in the cells may have one or more mutation, such as a point mutation, small deletion, etc.