Knockdown of ACAT-1 reduces amyloidogenic processing of APP
Knockdown of ACAT-1 reduces amyloidogenic processing of APP
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DOI：
10.1016/j.febslet.2007.03.056
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发表时间：
2007-04-17
期刊：
影响因子：
3.5
通讯作者：
Kovacs, Dora M.
中科院分区：
文献类型：
--
作者：
Huttunen, Henri J.;Greco, Christopher;Kovacs, Dora M.
先前的研究表明，在阿尔茨海默病的细胞和动物模型中，酰基辅酶A：胆固醇酰基转移酶（ACAT），一种控制游离胆固醇和胆固醇酯之间细胞平衡的酶，调节APP的蛋白水解过程。在这里，我们报告了ACAT-1 RNAi使细胞ACAT-1蛋白降低了50%，胆固醇酯水平降低了22%，同时导致内质网膜游离胆固醇含量略有增加。这与APP蛋白水解过程减少和A β分泌减少40%相关。这些数据表明，即使ACAT活性的适度降低也会对a β的产生产生强大的抑制作用。(c) 2007年欧洲生化学会联合会。Elsevier B.V.版权所有。
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.