The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: Implications for Alzheimer's disease

被引：105

作者：

Placido, A. I. ^{[1
,2
,3
]}

Pereira, C. M. F. ^{[1
,2
,3
]}

Duarte, A. I. ^{[1
,2
,4
]}

Candeias, E. ^{[1
,2
,4
]}

Correia, S. C. ^{[1
,2
,4
]}

Santos, R. X. ^{[1
,2
,5
]}

Carvalho, C. ^{[1
,2
,4
]}

Cardoso, S. ^{[1
,2
,4
]}

Oliveira, C. R. ^{[1
,2
,3
]}

Moreira, P. I. ^{[1
,2
,3
]}

机构：

[1] Univ Coimbra, Fac Med, Inst Physiol, P-3004517 Coimbra, Portugal

[2] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal

[3] Univ Coimbra, Fac Med, P-3004517 Coimbra, Portugal

[4] Univ Coimbra, Inst Interdisciplinary Res, P-3004517 Coimbra, Portugal

[5] Univ Coimbra, Dept Life Sci, P-3004517 Coimbra, Portugal

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2014年 / 1842卷 / 09期

关键词：

Alzheimer's disease; amyloid precursor protein; endoplasmic reticulum; secretory pathway; therapeutic targets; trafficking; ALPHA-SECRETASE CLEAVAGE; ER-STRESS; CELL-DEATH; MOLECULAR CHAPERONE; NEURONAL INJURY; QUALITY-CONTROL; BETA-SECRETASE; MICE LACKING; APP; ACTIVATION;

D O I：

10.1016/j.bbadis.2014.05.003

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：

The endoplasmic reticulum (ER) is the principal organelle responsible for the proper folding/processing of nascent proteins and perturbed ER function leads to a state known as ER stress. Mammalian cells try to overcome ER stress through a set of protein signaling pathways and transcription factors termed the unfolded protein response (UPR). However, under unresolvable ER stress conditions, the UPR is hyperactivated inducing cell dysfunction and death. The accumulation of misfolded proteins in the brain of Alzheimer's disease (AD) patients suggests that alterations in ER homeostasis might be implicated in the neurodegenerative events that characterize this disorder. This review discusses the involvement of ER stress in the pathogenesis of AD, focusing the processing and trafficking of the AD-related amyloid precursor protein (APP) during disease development. The potential role of ER as a therapeutic target in AD will also be debated. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：1444 / 1453

页数：10

共 119 条

[1] Activating transcription factor 4 [J].