Human neprilysin is capable of degrading amyloid β peptide not only in the monomeric form but also the pathological oligomeric form

• Published in: Neuroscience letters 2003-10, Vol.350 (2), p.113-116
• Main Authors: Kanemitsu, Hyoe, Tomiyama, Takami, Mori, Hiroshi
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - metabolism; Amyloid β1–40; Amyloid β1–42; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - pathology; Cell Line; Enzyme Inhibitors - pharmacology; Humans; Medical sciences; Monomer; Neprilysin; Neprilysin - antagonists & inhibitors; Neprilysin - chemistry; Neprilysin - metabolism; Neuropharmacology; Oligomer; Peptide Fragments - metabolism; Peptide Hydrolases - metabolism; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; RNA, Messenger - metabolism
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(03)00898-X

Amyloid β-peptide (Aβ) is widely believed to play a central role in Alzheimer's disease (AD). Coordinate regulation of cerebral Aβ level is important in the pathogenesis of AD since either increased production of Aβ from amyloid precursor protein or decreased degradation causes elevated levels of Aβ, leading to accumulation of cerebral plaque formation or amyloid angiopathy. Here we studied neprilysin, a putative proteolytic enzyme for Aβ, and found that it degraded not only monomeric but also oligomeric forms of Aβ1–40. Moreover, neprilysin was found to be capable of degradation of the oligomeric form of Aβ1–42, a significant Aβ species in early pathogenesis. Neprilysin to decrease cerebral Aβ is suggested to be inevitable factor as a vital therapeutic target.