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BACE1 Inhibition by Genistein: Biological Evaluation, Kinetic Analysis, and Molecular Docking Simulation

Journal of Medicinal Food 2018년 21권 4호 p.416 ~ 420
윤금주, 박지현, 이선아, 이진혁, 윤은영, 정우식, 전미라,
소속 상세정보
윤금주 ( Youn Kum-Ju ) - Dong-A University Department of Food Science and Nutrition
박지현 ( Park Ji-Hyun ) - Dong-A University Department of Food Science and Nutrition
이선아 ( Lee Seon-Ah ) - Dong-A University Department of Food Science and Nutrition
이진혁 ( Lee Jin-Hyuk ) - Dong-A University Department of Food Science and Nutrition
윤은영 ( Yun Eun-Young ) - Sejong University Korea Graduate School of Integrated Bioindustry
정우식 ( Jeong Woo-Sik ) - Inje University College of Biomedical Science and Engineering Department of Food and Life Sciences
전미라 ( Jun Mi-Ra ) - Dong-A University Department of Food Science and Nutrition

Abstract


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.

키워드

Alzheimer’s disease; β-secretase (BACE1); genistein; in silico molecular docking; isoflavones

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