Induction of the unfolded protein response by α-synuclein in experimental models of Parkinson's disease

被引：187

作者：

Bellucci, Arianna ^{[1
]}

Navarria, Laura ^{[1
]}

Zaltieri, Michela ^{[1
]}

Falarti, Elisa ^{[1
]}

Bodei, Serena ^{[1
]}

Sigala, Sandra ^{[1
]}

Battistin, Leontino ^{[2
]}

Spillantini, MariaGrazia ^{[3
]}

Missale, Cristina ^{[1
]}

Spano, PierFranco ^{[1
]}

机构：

[1] Univ Brescia, Dept Biomed Sci & Biotechnol, Div Pharmacol, I-25123 Brescia, Italy

[2] IRCCS S Camillo Hosp, Venice, Italy

[3] Univ Cambridge, Brain Repair Ctr, Dept Clin Neurosci, Cambridge, England

来源：

JOURNAL OF NEUROCHEMISTRY | 2011年 / 116卷 / 04期

关键词：

alpha-synuclein; ATF4; CREB-2; cytochrome c; GRP78; BiP; Parkinson's disease; unfolded protein response; ENDOPLASMIC-RETICULUM STRESS; CELL-DEATH; ER STRESS; AUTOPHAGY; ACTIVATION;

D O I：

10.1111/j.1471-4159.2010.07143.x

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：

P>Accumulation of misfolded proteins in the endoplasmic reticulum (ER) is the main event leading to the induction of the ER stress-related unfolded protein response (UPR). Recent postmortem evaluation, showing that the UPR pathway is activated in nigral dopaminergic neurons bearing alpha-synuclein inclusions in the brain of Parkinson's disease (PD) patients, suggests that the activation of the UPR may be induced by the accumulation of alpha-synuclein. In this study, we show that the misfolded protein-sensor/UPR activator glucose-regulated protein 78/immunoglobulin heavy chain-binding protein was bound to alpha-synuclein and was increased in 'in vitro' and 'in vivo' models showing aggregated alpha-synuclein accumulation. Moreover, alpha-synuclein accumulation induced the expression of the UPR-related activating transcription factor 4/cAMP-responsive element-2. These findings indicate that activation of the UPR pathway in the PD brain is associated with alpha-synuclein accumulation occurring in part within the ER.

引用

页码：588 / 605

页数：18

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