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 present invention provides a method of assaying for and arresting, preventing and/or reversing the impairment of central and peripheral nervous system function comprising reducing &bgr;-amyloid plaque burden by the administration of compounds that reduce apoE expression. The compounds used in the method of the invention may be: 1) inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase; 2) inhibitors of cholesterol biosynthesis; 3) inhibitors of protein isoprenylation, specifically geranylgeranylation; and/or 4) inhibitors of NF-&kgr;B activation or function. Assays for compounds with inhibit apoE expression from microglial cells are also disclosed.

Abstract: The present invention provides a method of assaying for and arresting, preventing and/or reversing the impairment of central and peripheral nervous system function comprising reducing &bgr;-amyloid plaque burden by the administration of compounds that reduce apoE expression. The compounds used in the method of the invention may be: 1) inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase; 2) inhibitors of cholesterol biosynthesis; 3) inhibitors of protein isoprenylation, specifically geranylgeranylation; and/or 4) inhibitors of NF-&kgr;B activation or function. Assays for compounds with inhibit apoE expression from microglial cells are also disclosed.

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 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.

Abstract: The present invention provides methods that can be used to identify &bgr;-amyloid reducing compounds. The present invention is based on the use of organotypic brain slice culturing methods to simultaneously assess the toxicity and &bgr;-amyloid reducing activity of a test compound.

Abstract: This invention relates to compounds and pharmaceutical compositions, and methods for inhibiting or preventing the amyloid protein deposits in the brain which are associated with Alzheimer's disease and aged Down's syndrome patients. More particularly, it relates to the treatment of Alzheimer's disease.

Abstract: Cloned recombinant or synthetic DNA sequences related to the pathology of Alzheimer's disease are injected into fertilized mammalian eggs (preferably mouse eggs). The injected eggs are implanted in pseudo pregnant females and are grown to term to provide transgenic mice whose cells express proteins related to the pathology of Alzheimer's disease. The injected sequences are constructed having promoter sequences connected so as to express the desired protein in specific tissues of the transgenic mammal (most notably in nerve tissue). The proteins which are preferably ubiquitously expressed include: (1) .beta.-amyloid core precursor proteins; (2) .beta.-amyloid related precursor proteins; and (3) serine protease inhibitor. The transgenic mice provide useful models for studying compounds being tested for their usefulness in treating Alzheimer's disease, and for studying the in vivo interrelationships of these proteins to each other.

Abstract: Recombinant materials for the production of low molecular weight hydrophobic lung surfactant proteins are disclosed and claimed. The monomeric forms of the proteins from human and canine sources have apparent molecular weights of about 5 kd and form dimers under some conditions. The availability of these recombinant materials permits production of large amounts of these proteins through recombinant techniques and permits the use of these proteins in pharmaceutical compositions in the treatment of respiratory deficiency syndromes.

Abstract: There are disclosed neurotrophic factors which are capable of being expressed as polypeptides lacking the microheterogeneity associated with a related native-sequence factor, CNTF. Also disclosed are DNA sequences encoding the neurotrophic factors and methods for expressing and recovering the factors as homogeneous polypeptides.

Abstract: The complete coding sequences and amino acid sequences for both canine and human 32K alveolar surfactant proteins (ASP) are disclosed; clones encoding variants of the SP-18 and SP-5 forms of human protein are disclosed. Methods and vectors for obtaining these proteins in recombinant form are also described. An improved method for purification of the 32K protein takes advantage of its carbohydrate affinity. Pharmaceutical compositions in the treatment of respiratory deficiency syndrome use the 10K proteins with or without the 32K form. Synthetic peptides based on the human SP-5 protein are provided as well, which peptides show significant ASP activity.

Abstract: Cloned recombinant or synthetic DNA sequences related to the pathology of Alzheimer's disease are injected into fertilized mouse eggs. The injected eggs are implanted in pseudo pregnant females and are grown to term to provide transgenic mice whose cells express proteins related to the pathology of Alzheimer's disease. The injected sequences are constructed having promoter sequences connected so as to express the desired protein in brain tissues of the transgenic mouse. The proteins which are preferably ubiquitously expressed include (1) .beta.-amyloid core precursor proteins; and (2) .beta.-amyloid related precursor proteins; and (3) serine protease inhibitor. The transgenic mice provide useful models for studying compounds being tested for their usefulness in treating Alzheimer's disease, and for studying the in vivo interrelationships of these proteins to each other.

Abstract: DNA sequences encoding .beta.-amyloid-related proteins associated with Alzheimer's disease are disclosed. Also provided herein is a DNA sequence encoding a novel protease inhibitor. These sequences are used in producing or constructing recombinant .beta.-amyloid core protein, .beta.-amyloid-related proteins and recombinant or synthetic immunogenic peptides. Antibodies generated against the recombinant proteins or immunogenic peptides derived therefrom can be used for cerebral fluid or serum protein diagnosis of Alzheimer's disease.

Abstract: The present invention provides an in vitro tissue culture-based assay for amyloid deposition specific for Alzheimer's disease which is suitable for routine drug screening analysis. Immunological diagnostic reagents for Alzheimer's disease are also provided.

Abstract: DNA sequences encoding the beta-amyloid core protein, and beta-amyloid-related proteins associated with Alzheimer's disease are disclosed. These sequences are used in producing or constructing recombinant beta-amyloid core protein, beta-amyloid-related proteins and recombinant or synthetic immunogenic peptides. These sequences are also used to identify genomic mutations and/or restriction site alterations which are associated with a predisposition to Alzheimer's disease, for purposes of genetic screening. Antibodies generated against the recombinant proteins or immunogenic peptides derived therefrom can be used for cerebral fluid or serum protein diagnosis of Alzheimer's disease.

Abstract: Pharmaceutical compositions containing a 57 amino acid protease inhibitor and uses for those compositions are taught. The protease inhibitor is referred to as A4i which is associated with Alzheimer's disease. In addition to the A4i protease, other analogs are taught as are pharmaceutical compositions containing such analogs and their uses in treating a variety of abnormalities associated with Kunitz-type basic protease inhibitors. For example, it has been found that pharmaceutical compositions containing A4i protease and analogs thereof inhibit plasmin and tryptase, and also inhibit pancreatic trypsin, alpha-chymotrypsin, tissue kallikrein and serum kallikrein. In that certain diseases are associated with a general release of proteases such as trypsin, chymotrypsin and elastase into the circulatory system pharmaceutical compositions containing A4i and analogs thereof can be used in the management of such diseases.

Abstract: The complete coding sequences and amino acid sequences for both canine and human 32K alveolar surfactant proteins (ASP) are disclosed; clones for the 10K protein have also been obtained. Methods and vectors for obtaining these proteins in recombinant form are described. The availability of large amounts of these proteins through recombinant techniques permits the use of ASP in suitable pharmaceutical compositions in the treatment of respiratory deficiency syndromes.

Abstract: Recombinant vaccines for immunizing horses against equine influenza virus (EIV) are disclosed. The DNA sequences encoding the hemagglutinin (HA) and neuraminidase (NA) glycoproteins from the two strains of EIV currently infective in horses are used to construct vaccinia carried vaccines, to design synthetic peptides for primer and booster administration, and to permit recombinant synthesis of HA and/or NA protein based vaccines. These DNA sequences also provide probes useful for preparing similar vaccines from fresh isolates of new strains generated by genetic drift.

Abstract: The complete coding sequences and amino acid sequences for both canine and human 32K alveolar surfactant proteins (ASP) are disclosed; clones for the 10K protein have also been obtained. Methods and vectors for obtaining these proteins in recombinant form are described. The availability of large amounts of these proteins through recombinant techniques permits the use of ASP in suitable pharmaceutical compositions in the treatment of respiratory deficiency syndromes.

Abstract: The complete coding sequences and amino acid sequences for both canine and human alveolar surfactant protein (ASP) are disclosed. Methods and vectors for obtaining these proteins in recombinant form are described. The availability of large amounts of these proteins through recombinant techniques permits the use of ASP in suitable pharmaceutical compositions in the treatment of respiratory deficiency syndromes.