Mitochondrial dysfunction in the limelight of Parkinson's disease pathogenesis.
Mitochondrial dysfunction in the limelight of Parkinson's disease pathogenesis.
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DOI：
10.1016/j.bbadis.2008.11.007
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发表时间：
2009-07
影响因子：
6.2
通讯作者：
Thomas, Bobby
中科院分区：
文献类型：
--
作者：
Banerjee, Rebecca;Starkov, Anatoly A.;Beal, M. Flint;Thomas, Bobby
关键词：
帕金森病（PD）是一种病因不明的进行性神经退行性运动障碍。它的特点是在大脑中广泛的神经变性，在黑质致密部的中脑A9多巴胺能神经元的严重损失。几种生化异常理论与帕金森病的发病机制有关，其中线粒体功能障碍是由于线粒体复合体I的损伤和随后的氧化应激，在帕金森病的实验模型和散发性疾病的死后组织中似乎占据了中心位置。最近对特定基因突变及其对线粒体功能的影响的鉴定进一步加强了线粒体异常在疾病发病机制中的相关性。在散发性和家族性帕金森病中，与疾病相关的线粒体异常模式包括线粒体电子传递链功能受损、线粒体DNA衰老相关损伤、钙缓冲功能受损以及线粒体形态和动力学异常。在这里，我们提供了在散发性和家族性PD中发挥疾病发病机制作用的特定线粒体功能的概述。我们建议利用这些获得的见解进一步简化和集中研究，以更好地了解线粒体在疾病发展中的作用，并利用潜在的线粒体靶点进行PD发病机制的治疗干预。
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.
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影响因子：
10.4
作者：
Brown TP;Rumsby PC;Capleton AC;Rushton L;Levy LS
通讯作者：
Levy LS
DOI：
10.1006/bbrc.2000.4113
发表时间：
2001-01-12
影响因子：
3.1
作者：
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影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
URBANOMARQUEZ, A
影响因子：
11.2
作者：
Biskup, Saskia;Moore, Darren J.;Dawson, Valina L.
通讯作者：
Dawson, Valina L.