title: BACE inhibitors as potential therapeutics for Alzheimer's disease.
abstract: Accumulation of Abeta peptide in the brain results in the formation of amyloid plaques characteristic of Alzheimer's disease (AD) pathology. Abeta soluble oligomers and protofibrils are neurotoxic and these are believed to be a major cause of neurodegeneration in AD. Abeta is derived from a precursor protein by two sequential cleavage steps involving beta- and gamma-secretases, two proteolytic enzymes that represent rational drug targets. beta-secretase was identified as the membrane-anchored aspartyl protease BACE (or BACE1) and found to be elevated in brain cortex of patients with sporadic Alzheimer's disease. In this review, we summarize current approaches towards the development of BACE inhibitors with focus on bioactive compounds and related patents. Recent reports have described drugs that are effective at inhibiting Abeta production in the brain of transgenic mouse models. The beginning of Phase I clinical trials has been approved for one of them and we can expect that in the near future BACE inhibitors will provide novel effective therapeutics to treat AD.
authors.affiliation: Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. gmevin@unimelb.edu.au
authors.forename: Genevieve
authors.initials: G
authors.lastname: Evin
authors.forename: Vijaya B
authors.initials: VB
authors.lastname: Kenche
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D005030:Ethylenes / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans
chemical_list: D004791:Enzyme Inhibitors; D005030:Ethylenes; C067254:hydroxyethylene; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human