Pathogenesis of Parkinson's Disease

被引：225

作者：

Hirsch, Etienne C. ^{[1
,2
,3
]}

Jenner, Peter ^{[4
]}

Przedborski, Serge ^{[5
,6
]}

机构：

[1] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, Hop Salpetriere, Paris, France

[2] INSERM, Unite Mixte Rech U975, Paris, France

[3] CNRS, Unite Mixte Rech 7225, Paris, France

[4] Kings Coll London, Neurodegenerat Dis Res Ctr, Inst Pharmaceut Sci, Sch Biomed Sci, London WC2R 2LS, England

[5] Columbia Univ, Dept Neurol, Dept Pathol & Cell Biol, New York, NY 10032 USA

[6] Columbia Univ, Ctr Motor Neuron Biol & Dis, New York, NY 10032 USA

来源：

MOVEMENT DISORDERS | 2013年 / 28卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Dopamine neuron; inflammation; neurodegeneration; mitochndria; misfolded protein; ALPHA-SYNUCLEIN; SUBSTANTIA-NIGRA; MOUSE MODEL; DOPAMINERGIC NEURODEGENERATION; NEURONS; PATHOLOGY; MITOCHONDRIA; CONTRIBUTES; RECRUITMENT; DYSFUNCTION;

D O I：

10.1002/mds.25032

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Parkinson's disease is a common adult-onset neurodegenerative disorder whose pathogenesis remains essentially unknown. Currently, it is believed that the neurodegenerative process in Parkinson's disease is a combination of both cell-autonomous and non-cell-autonomous mechanisms. Proposed cell-autonomous mechanisms include alterations in mitochondrial bioenergetics,dysregulation of calcium homeostasis, and impaired turnover of mitochondria. As for the proposed non-cell-autonomous mechanisms, they involve prion-like behavior of misfolded proteins and neuroinflammation. This suggests that cell death in Parkinson's disease is caused by a multifactorial cascade of pathogenic events and argues that effective neuroprotective therapy for Parkinson's disease may have to rely on multiple drug interventions. (C) 2013 Movement Disorder Society

引用

页码：24 / 30

页数：7

共 54 条

[1] Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission [J].

Alvarez-Erviti, Lydia ;

Seow, Yiqi ;

Schapira, Anthony H. ;

Gardiner, Chris ;

Sargent, Ian L. ;

Wood, Matthew J. A. ;

Cooper, J. Mark .

NEUROBIOLOGY OF DISEASE, 2011, 42 (03) :360-367

[2] Transcriptional coactivator PGC-1α controls the energy state and contractile function of cardiac muscle [J].

Arany, Z ;

He, HM ;

Lin, JD ;

Hoyer, K ;

Handschin, C ;

Toka, O ;

Ahmad, F ;

Matsui, T ;

Chin, S ;

Wu, PH ;

Rybkin, II ;

Shelton, JM ;

Manieri, M ;

Cinti, S ;

Schoen, FJ ;

Bassel-Duby, R ;

Rosenzweig, A ;

Ingwall, JS ;

Spiegelman, BM .

CELL METABOLISM, 2005, 1 (04) :259-271

[3] Evidence of active microglia in substantia nigra pars compacta of parkinsonian monkeys 1 year after MPTP exposure [J].

Barcia, C ;

Bahillo, AS ;

Fernández-Villalba, E ;

Bautista, V ;

Poza, MPY ;

Fernández-Barreiro, A ;

Hirsch, EC ;

Herrero, MT .

GLIA, 2004, 46 (04) :402-409

[4] High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease [J].

Bender, A ;

Krishnan, KJ ;

Morris, CM ;

Taylor, GA ;

Reeve, AK ;

Perry, RH ;

Jaros, E ;

Hersheson, JS ;

Betts, J ;

Klopstock, T ;

Taylor, RW ;

Turnbull, DM .

NATURE GENETICS, 2006, 38 (05) :515-517

[5] Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease [J].

Benner, EJ ;

Mosley, RL ;

Destache, CJ ;

Lewis, TB ;

Jackson-Lewis, V ;

Gorantla, S ;

Nemachek, C ;

Green, SR ;

Przedborski, S ;

Gendelman, HE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (25) :9435-9440

[6] Viral vector-mediated overexpression of α-synuclein as a progressive model of Parkinson's disease [J].

Bjorklund, Anders ;

Cenci, M. Angela .

RECENT ADVANCES IN PARKINSONS DISEASE: TRANSLATIONAL AND CLINICAL RESEARCH, 2010, 184 :89-111

[7] Staging of brain pathology related to sporadic Parkinson's disease [J].

Braak, H ;

Del Tredici, K ;

Rüb, U ;

de Vos, RAI ;

Steur, ENHJ ;

Braak, E .

NEUROBIOLOGY OF AGING, 2003, 24 (02) :197-211

[8] Protective action of the peroxisome proliferator-activated receptor-γ agonist pioglitazone in a mouse model of Parkinson's disease [J].

Breidert, T ;

Callebert, J ;

Heneka, MT ;

Landreth, G ;

Launay, JM ;

Hirsch, EC .

JOURNAL OF NEUROCHEMISTRY, 2002, 82 (03) :615-624

[9] Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease [J].

Brochard, Vanessa ;

Combadiere, Behazine ;

Prigent, Annick ;

Laouar, Yasmina ;

Perrin, Aline ;

Beray-Berthat, Virginie ;

Bonduelle, Olivia ;

Alvarez-Fischer, Daniel ;

Callebert, Jacques ;

Launay, Jean-Marie ;

Duyckaerts, Charles ;

Flavell, Richard A. ;

Hirsch, Etienne C. ;

Hunot, Stephane .

JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (01) :182-192

[10] 'Rejuvenation' protects neurons in mouse models of Parkinson's disease [J].

Chan, C. Savio ;

Guzman, Jaime N. ;

Ilijic, Ema ;

Mercer, Jeff N. ;

Rick, Caroline ;

Tkatch, Tatiana ;

Meredith, Gloria E. ;

Surmeier, D. James .

NATURE, 2007, 447 (7148) :1081-U5

← 1 2 3 4 5 6 →