Knockdown of ACAT-1 reduces amyloidogenic processing of APP

被引：45

作者：

Huttunen, Henri J. ^{[1
]}

Greco, Christopher ^{[1
]}

Kovacs, Dora M. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp,MassGen Inst Neurodegenera, Neurobiol Dis Lab,Genet & Aging Res Unit, Charlestown, MA 02129 USA

来源：

FEBS LETTERS | 2007年 / 581卷 / 08期

关键词：

RNAi; cholesterol; cholesteryl esters; amyloid-beta; Alzheimer's disease; amyloid precursor protein; ACAT;

D O I：

10.1016/j.febslet.2007.03.056

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Previous studies have shown that acyl-coenzyme A:cholesterol acyl transferase (ACAT), an enzyme that controls cellular equilibrium between free cholesterol and cholesteryl esters, modulates proteolytic processing of APP in cell-based and animal models of Alzheimer's disease. Here we report that ACAT-1 RNAi reduced cellular ACAT-1 protein by similar to 50% and cholesteryl ester levels by 22% while causing a slight increase in the free cholesterol content of ER membranes. This correlated with reduced proteolytic processing of APP and 40% decrease in A beta secretion. These data show that even a modest decrease in ACAT activity can have robust suppressive effects on A beta generation. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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收藏

页码：1688 / 1692

页数：5

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