Biological evaluation and in silico docking study of γ-linolenic acid as a potential BACE1 inhibitor

被引：13

作者：

Youn, Kumju ^{[1
]}

Lee, Jinhyuk ^{[2
,3
]}

Yun, Eun-Young ^{[4
]}

Ho, Chi-Tang ^{[5
]}

Karwe, Mukund V. ^{[5
]}

Jeong, Woo-Sik ^{[6
]}

Jun, Mira ^{[1
]}

机构：

[1] Dong A Univ, Dept Food Sci & Nutr, Pusan 604714, South Korea

[2] Korea Res Inst Biosci & Biotechnol, Korean Bioinforrnat Ctr, Taejon 305806, South Korea

[3] Univ Sci & Technol, Dept Bioinformat, Taejon 305350, South Korea

[4] Natl Acad Agr Sci RDA, Dept Agr Biol, Suwon 441100, South Korea

[5] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA

[6] Inje Univ, Coll Biomed Sci & Engn, Dept Food & Life Sci, Gimhae 621749, South Korea

来源：

JOURNAL OF FUNCTIONAL FOODS | 2014年 / 10卷

关键词：

Alzheimer's disease; beta-secretase (BACE1); beta-amyloid peptide (A beta); gamma-linolenic acid; MICROVESSEL ENDOTHELIAL-CELLS; EVENING PRIMROSE OIL; BETA-SECRETASE; ALZHEIMERS-DISEASE; HUMAN BRAIN; FATTY-ACID; EXPRESSION; TRANSPORT; RATS;

D O I：

10.1016/j.jff.2014.06.005

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

Sequential proteolytic cleavage of amyloid precursor protein (APP) by beta-secretase (BACE1) is a crucial process in beta-amyloid peptide (A beta) generation, which further forms into neurotoxic amyloid plaques that are considered to be a pivotal hallmark in the development and progress of Alzheimer's disease (AD). Hence, the inhibition of BACE1 has emerged as a credible target for the prevention and/or treatment of AD. In this study, gamma-linolenic acid (GLA) was discovered as a novel BACE1 specific inhibitor. GLA non-competitively suppressed BACE1 activity with an IC50 value of 7.6 x 10(-5) M and K-i value of 3.5 x 10(-5) M. In addition, we demonstrated the calculated docking poses of GLA to human BACE1 and revealed the interactions of GLA with the allosteric site of the enzyme bound with the OH group of CYS359. Our findings provide a novel possibility of GLA to be efficacious for the prevention of AD and provide scaffolds to explore more potent natural BACE1 inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：187 / 191

页数：5

共 30 条

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