染料木素
甘氨酸
大豆黄酮
化学
对接(动物)
异黄酮素
变构调节
酶
生物化学
生物杀虫素A
药理学
生物
医学
内分泌学
护理部
作者
Kumju Youn,Jihyun Park,Seonah Lee,Seung‐Eun Lee,Jinhyuk Lee,Eun‐Young Yun,Woo-Sik Jeong,Mira Jun
出处
期刊:Journal of Medicinal Food
[Mary Ann Liebert]
日期:2018-04-01
卷期号:21 (4): 416-420
被引量:32
标识
DOI:10.1089/jmf.2017.4068
摘要
β-site amyloid precursor protein cleaving enzyme 1 (BACE1) plays a role in generating amyloid β (Aβ), thus playing a major part early in the pathogenesis of Alzheimer's disease (AD). BACE1 has emerged as a crucial therapeutic target for decreasing the Aβ concentration in the AD brain. To explore natural BACE1 inhibitors, the present study concentrated on isoflavones, including genistein, formononetin, glycitein, daidzein, and puerarin. In this study, in vitro anti-AD activities were assessed using BACE1 inhibition assays, as well as enzyme kinetic predictions. Molecular docking analysis was applied to design potential BACE1 inhibitors. Among the major isoflavones, genistein exerted a notable BACE1 inhibition through reversible noncompetitive mechanism, while other compounds were less potent against BACE1. The docking study revealed that genistein had negative binding energy (−8.5 kcal/mol) and was stably positioned in the allosteric domains of BACE1 residues. It interacted with important amino acid residues in BACE1, such as ASN37, GLN73, and TRP76, through hydrogen bonding. The results suggested that genistein may be beneficial for preventing and/or treating AD. Furthermore, it may provide potential guidelines for the design of new BACE1 inhibitors.
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