Mitochondrial dysfunction in the limelight of Parkinson's disease pathogenesis

被引:187
作者
Banerjee, Rebecca [1 ]
Starkov, Anatoly A. [1 ]
Beal, M. Flint [1 ]
Thomas, Bobby [1 ]
机构
[1] Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2009年 / 1792卷 / 07期
基金
美国国家卫生研究院;
关键词
Mitochondrial dysfunction; Mitochondrial DNA; Electron transport chain; Permeability transition pore; alpha-synuclein; Parkin; PINK1; DJ-1; LRRK2; PERMEABILITY TRANSITION PORE; COMPLEX-I DEFICIENCY; EARLY-ONSET PARKINSONISM; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; ADENINE-NUCLEOTIDE TRANSLOCASE; ENVIRONMENTAL RISK-FACTORS; RESPIRATORY-CHAIN ACTIVITY; SYNUCLEIN TRANSGENIC MICE; ELECTRON-TRANSPORT CHAIN; SUBSTANTIA-NIGRA NEURONS;
D O I
10.1016/j.bbadis.2008.11.007
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
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder with unknown etiology. It is marked by widespread neurodegeneration in the brain with profound loss of A9 midbrain dopaminergic neurons in substantia nigra pars compacta. Several theories of biochemical abnormalities have been linked to pathogenesis of PD of which mitochondrial dysfunction due to an impairment of mitochondrial complex I and subsequent oxidative stress seems to take the center stage in experimental models of PD and in postmortem tissues of sporadic forms of illness. Recent identification of specific gene mutations and their influence on mitochondrial functions has further reinforced the relevance of mitochondrial abnormalities in disease pathogenesis. In both sporadic and familial forms of PD abnormal mitochondrial paradigms associated with disease include impaired functioning of the mitochondrial electron transport chain, aging associated damage to mitochondrial DNA, impaired calcium buffering, and anomalies in mitochondrial morphology and dynamics. Here we provide an overview of specific mitochondrial functions affected in sporadic and familial PD that play a role in disease pathogenesis. We propose to utilize these gained insights to further streamline and focus the research to better understand mitochondria's role in disease development and exploit potential mitochondrial targets for therapeutic interventions in PD pathogenesis. Published by Elsevier B.V.
引用
收藏
页码:651 / 663
页数:13
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