Redox imbalance in Parkinson's disease

被引:219
作者
Chinta, Shankar J. [1 ]
Andersen, Julie K. [1 ]
机构
[1] Buck Inst Age Res, Novato, CA 94945 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2008年 / 1780卷 / 11期
基金
美国国家卫生研究院;
关键词
Parkinson's disease; dopaminergic neuron; glutathione; iron; oxidative stress; mitochondrial dysfunction;
D O I
10.1016/j.bbagen.2008.02.005
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 an adult-onset neurodegenerative disorder characterized by preferential loss of dopaminergic neurons in an area of the midbrain called the substantia nigra (SN) along with occurrence of intraneuronal inclusions called Lewy bodies. The majority of cases of PD are sporadic in nature with late onset (95% of patients); however a few PD cases (5%) are seen in familial clusters with generally earlier onset. Although PD has been heavily researched, so far the exact cause of the rather selective cell death is unknown. Multiple lines of evidence suggest an important role for oxidative stress. Dopaminergic neurons (DA) are particularly prone to oxidative stress due to DA metabolism and auto-oxidation combined with increased iron, decreased total glutathione levels and mitochondrial complex I inhibition-induced ROS production in the SN which can lead to cell death by exceeding the oxidative capacity of DA-containing cells in the region. Enhancing antioxidant capabilities and chelating labile iron pools in this region therefore constitutes a rational approach to prevent or slow ongoing damage of DA neurons. In this review, we summarize the various sources of reactive oxygen species that may cause redox imbalance in PD as well as potential therapeutic targets for attenuation of oxidative stress associated with PD. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:1362 / 1367
页数:6
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