Abstract: Disclosed are compounds which bind ?4 integrins, where the ?4 integrin is preferably VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by ?4 integrins, where the ?4 integrin is preferably VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: The application provides novel neuroactive fragments of human amyloid precursor protein (APP). The fragments include sequence from the A? region of APP but also extend upstream. The fragments are soluble in aqueous solution most bands are about 10 kDa and above and do not correspond with the expected molecular weight of a dimer or trimer. The fragments and subfragments thereof can be used as immunogens in methods of immunotherapy to treat Alzheimer's and other amyloidogenic diseases characterized by deposits of A? in the brain. Antibodies to the part of the fragment upstream from APP or the interface between A? and the upstream sequence can also be used in such therapeutic method. The fragments are also useful as markers, which can be detected for diagnosis or prognosis of disease or for screening agents.

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

Abstract: Disclosed are compounds of the formula and the pharmaceutically acceptable salts thereof wherein the variables G, L, A, W, E, R2, R3, R4, R5, RN, and Rc are defined herein. These compounds interact with and inhibit the activity of the enzyme beta-secretase. These compounds are therefore useful in treating Alzheimer's disease and other similar diseases. Pharmaceutical compositions and methods of treatment of these diseases are also disclosed.

Abstract: The invention provides transgenic animals that are heterozygous or homozygous for a nonfunctional allele of BACE-1. These animals show normal development indicating that BACE-1 is not necessary for development and hence is an appropriate therapeutic target. The transgenic animals are useful in various screening assays including identifying inhibitors of other enzymes involved in processing of APP to A? and determining a toxicity profile of inhibitors of BACE-1.

Abstract: The application identifies fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

Abstract: The present invention relates to compounds of formula (AA) (I) and (X): useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Abstract: Disclosed are a series of phenylalanine derivatives, to compositions containing them, to processes for their preparation, and to their use in medicine.

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds aslo inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: Disclosed are various forms of an active, isolated ?-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (?-APPwt and ?-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate ?-secretase. Inhibitors of ?-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

Abstract: Dipeptide derived inhibitors of the ?-secretase enzyme are provided which are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A? peptide in a mammal. The compounds of the invention provide useful methods of treatment by administration of these inhibitors to reduce A? peptide formation and in pharmaceutical compositions.

Abstract: The present invention relates to compounds of formula (I) useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Abstract: The present invention relates to recombinant human BACE polypeptides. More particularly, the invention relates to recombinant human BACE polypeptides that have a modified amino acid sequence at position 33 of the BACE sequence, as well as to polynucleotides, expression vectors, host cells, and methods for producing the modified recombinant human BACE polypeptides.

Abstract: The invention provides to assays for agent useful for treatment of Parkinson's Disease. Included are cell-based assays for agents that modulate the effect of Parkin proteins on proteasome function. The invention also provides recombinant, enzymatically active, Parkin protein produced in prokaryotic expression systems, such as E. coli cells. Methods for purification of Parkin protein are also provided.

Abstract: The present invention is direct to a method of producing analgesia in a mammalian subject. The method includes administering to the subject an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivicaine, clonidine, hydromorphone, baclofen, fentanyil, buprenorphine, and sufentanil, or its pharmaceutically acceptable salts thereof, wherein the ?-conopeptide retains its potency and is physically and chemically compatible with the analgesic compound. A preferred route of administration is intrathecal administration, particularly continuous intrathecal infusion. The present invention is also directed to a pharmaceutical formulation comprising an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivicaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil.

Abstract: The present invention relates to compounds of formula (I): useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Abstract: Disclosed are various forms of an active, isolated ?-secretase enzyme in purified and recombinant form. This enzyme is implicated in the production of amyloid plaque components which accumulate in the brains of individuals afflicted with Alzheimer's disease. Recombinant cells that produce this enzyme either alone or in combination with some of its natural substrates (?-APPwt and ?-APPsw) are also disclosed, as are antibodies directed to such proteins. These compositions are useful for use in methods of selecting compounds that modulate ?-secretase. Inhibitors of ?-secretase are implicated as therapeutics in the treatment of neurodegenerative diseases, such as Alzheimer's disease.

Abstract: This invention is directed to acylated amino acid amidyl pyrazoles and related compounds of Formula I. The invention is also directed to a pharmaceutical formation comprising such compound or in a pharmaceutically acceptable salt form thereof. The invention is further directed to a method for inhibiting ?-amyloid peptide release and/or synthesis, a method for inhibiting ?-secretase activity, and a method for treating neurological disorders associated with ?-amyloid peptide production. The method comprises administering to a host a pharmaceutical formulation comprising an effective amount of a compound of Formula I. The compounds of Formula I are useful in the prevention and treatment of Alzheimer's disease.

Abstract: The invention provides transgenic non-human animals and transgenic non-human mammalian cells harboring a transgene encoding an APP polypeptide comprising the Swedish mutation.