title: Human neprilysin is capable of degrading amyloid beta peptide not only in the monomeric form but also the pathological oligomeric form.
abstract: Amyloid beta-peptide (Abeta) is widely believed to play a central role in Alzheimer's disease (AD). Coordinate regulation of cerebral Abeta level is important in the pathogenesis of AD since either increased production of Abeta from amyloid precursor protein or decreased degradation causes elevated levels of Abeta, leading to accumulation of cerebral plaque formation or amyloid angiopathy. Here we studied neprilysin, a putative proteolytic enzyme for Abeta, and found that it degraded not only monomeric but also oligomeric forms of Abeta1-40. Moreover, neprilysin was found to be capable of degradation of the oligomeric form of Abeta1-42, a significant Abeta species in early pathogenesis. Neprilysin to decrease cerebral Abeta is suggested to be inevitable factor as a vital therapeutic target.
authors.affiliation: Department of Neuroscience, Graduate School of Medicine Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Hyoe
authors.initials: H
authors.lastname: Kanemitsu
authors.forename: Takami
authors.initials: T
authors.lastname: Tomiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D012333:RNA, Messenger; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D010447:Peptide Hydrolases; D015260:Neprilysin