Lipoprotein receptors and cholesterol in APP trafficking and proteolytic processing, implications for Alzheimer's disease

被引：86

作者：

Marzolo, Maria-Paz ^{[2
,3
]}

Bu, Guojun ^{[1
,4
,5
]}

机构：

[1] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA

[2] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Biol Celular & Mol, FONDAP Ctr Cell Regulat & Pathol CRCP, Santiago, Chile

[3] MIFAB, Santiago, Chile

[4] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA

来源：

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY | 2009年 / 20卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Lipoprotein receptors; Cholesterol; Amyloid precursor protein; Amyloid-beta peptide; Alzheimer's disease; AMYLOID-PRECURSOR-PROTEIN; APOLIPOPROTEIN-E RECEPTOR-2; GAMMA-SECRETASE ACTIVITY; A-BETA PRODUCTION; TRANSGENIC MOUSE MODEL; LONG-TERM POTENTIATION; LIVER-X-RECEPTORS; CELL-SURFACE; LIPID RAFTS; APOE RECEPTOR;

D O I：

10.1016/j.semcdb.2008.10.005

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Amyloid-beta (A beta) peptide accumulation in the brain is central to the pathogenesis of Alzheimer's disease (AD). A beta is produced through proteolytic processing of a transmembrane protein, beta-amyloid precursor protein (APP), by beta- and gamma-secretases. Mounting evidence has demonstrated that alterations in APP cellular trafficking and localization directly impact its processing to A beta. Members of the low-density lipoprotein receptor family, including LRP, LRP1B, SorLA/LR11, and apoER2, interact with APP and regulate its endocytic trafficking. Additionally, APP trafficking and processing are greatly affected by cellular cholesterol content. In this review, we summarize the current understanding of the roles of lipoprotein receptors and cholesterol in APP trafficking and processing and their implication for AD pathogenesis and therapy. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：191 / 200

页数：10

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