Kanemitsu Hyoe, Tomiyama Takami, Mori Hiroshi
Department of Neuroscience, Graduate School of Medicine Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Neurosci Lett. 2003 Oct 23;350(2):113-6. doi: 10.1016/s0304-3940(03)00898-x.
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.
人们普遍认为β-淀粉样肽（Aβ）在阿尔茨海默病（AD）中起核心作用。由于淀粉样前体蛋白产生的Aβ增加或降解减少都会导致Aβ水平升高，进而导致脑斑块形成或淀粉样血管病的积累，因此大脑Aβ水平的协调调节在AD的发病机制中很重要。在此，我们研究了中性内肽酶（neprilysin），一种假定的Aβ蛋白水解酶，发现它不仅能降解Aβ1-40的单体形式，还能降解其寡聚体形式。此外，还发现中性内肽酶能够降解Aβ1-42的寡聚体形式，这是早期发病机制中的一种重要Aβ种类。中性内肽酶被认为是降低大脑Aβ水平的一个不可或缺的因素，是一个至关重要的治疗靶点。
