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

被引：188

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

共 50 条

[31] Perampanel Inhibits α-Synuclein Transmission in Parkinson's Disease Models
Ueda, Jun
Uemura, Norihito
Sawamura, Masanori
Taguchi, Tomoyuki
Ikuno, Masashi
Kaji, Seiji
Taruno, Yosuke
Matsuzawa, Shuichi
Yamakado, Hodaka
Takahashi, Ryosuke
MOVEMENT DISORDERS, 2021, 36 (07) : 1554 - 1564
[32] Experimental models of Parkinson's disease
Jenner, P
PARKINSON'S DISEASE, 2002, 1 : 39 - 50
[33] Experimental models of Parkinson's disease
M. Flint Beal
Nature Reviews Neuroscience, 2001, 2 : 325 - 332
[34] Experimental models of Parkinson's disease
Beal, MF
NATURE REVIEWS NEUROSCIENCE, 2001, 2 (05) : 325 - 332
[35] Unfolded Protein Response and Macroautophagy in Alzheimer's, Parkinson's and Prion Diseases
Milisav, Irina
Suput, Dusan
Ribaric, Samo
MOLECULES, 2015, 20 (12) : 22718 - 22756
[36] Experimental animal models of Parkinson's disease: A transition from assessing symptomatology to α-synuclein targeted disease modification
Ko, Wai Kin D.
Bezard, Erwan
EXPERIMENTAL NEUROLOGY, 2017, 298 : 172 - 179
[37] α-Synuclein in Parkinson's Disease
Stefanis, Leonidas
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2012, 2 (02):
[38] α-Synuclein and Parkinson's disease
Burke, RE
BRAIN RESEARCH BULLETIN, 1999, 50 (5-6) : 465 - 466
[39] α-synuclein and Parkinson's disease
Iwatsubo, T
SEIKAGAKU, 2002, 74 (06): : 477 - 482
[40] The first look at the morphing of α-synuclein protein in Parkinson's disease
Raison, Claire
EXPERT REVIEW OF PROTEOMICS, 2013, 10 (05) : 411 - 411

← 1 2 3 4 5 →