Biogenesis and metabolism of Alzheimer's disease Abeta amyloid peptides.
Biochemical and genetic evidence indicates the balance of biogenesis/clearance of Abeta amyloid peptides is altered in Alzheimer's disease. Abeta is derived, by two sequential cleavages, from the receptor-like amyloid precursor protein (APP). The proteases involved are beta-secretase, identified as the novel aspartyl protease BACE, and gamma-secretase, a multimeric complex containing the presenilins (PS). Gamma-secretase can release either Abeta40 or the more aggregating and cytotoxic Abeta42. Secreted Abeta peptides become either degraded by the metalloproteases insulin-degrading enzyme (IDE) and neprilysin or metabolized through receptor uptake mediated by apolipoprotein E. Therapeutic approaches based on secretase inhibition or amyloid clearance are currently under development.
Department of Pathology, The University of Melbourne and Mental Health Research Institute, Parkville, Vic. 3010, Australia. gmevin@unimelb.edu.au.
Geneviève
G
Evin
Andreas
A
Weidemann
D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011480:Protease Inhibitors; D010450:Endopeptidases