title: Potential treatment opportunities for Alzheimer's disease through inhibition of secretases and Abeta immunization.
abstract: Research over the past ten years on Alzheimer's disease has pursued many opportunities. Notable amongst the various approaches are efforts related to the "amyloid hypothesis." This hypothesis posits that the beta amyloid peptide causes the extensive neuropathology and clinical decline associated with the disease. Extensive research in this area has shown that the beta amyloid peptide is produced by proteases termed "secretases" and it has been shown that blockade of secretase functions reduce the amount of beta amyloid peptide produced. An additional approach to reduce beta amyloid, through an increase in clearance mechanisms, is to immunize with the peptide itself and induce an antibody response. The specifically elicited antibodies then bind to and stimulate clearance of the peptide from the brain. These findings have stimulated several approaches to develop novel therapeutic strategies to treat Alzheimer's disease that either are about or have entered the clinic.
authors.affiliation: Elan Pharmaceuticals, San Francisco, CA 94080, USA. dale.schenk@elancorp.com
authors.forename: D
authors.initials: D
authors.lastname: Schenk
authors.forename: D
authors.initials: D
authors.lastname: Games
authors.forename: P
authors.initials: P
authors.lastname: Seubert
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000276:immunology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D051379:Mice
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse