Mitochondria, oxidative stress and neurodegeneration
Mitochondria, oxidative stress and neurodegeneration
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DOI：
10.1016/j.jns.2012.05.030
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发表时间：
2012-11-15
影响因子：
4.4
通讯作者：
Radi, Elena
中科院分区：
文献类型：
--
作者：
Federico, Antonio;Cardaioli, Elena;Radi, Elena
线粒体参与通过氧化磷酸化（OXPHOS）向细胞供应ATP、关键分子的合成和对氧化应激的响应以及细胞凋亡。它们含有许多氧化还原酶，并且天然存在的氧化磷酸化效率低下会产生活性氧（ROS）。中枢神经系统的功能在很大程度上依赖于有效的线粒体功能，因为脑组织具有高能量需求。线粒体DNA（mtDNA）的突变、ROS的产生和存在以及环境因素可能导致能量衰竭并导致神经退行性疾病。许多罕见的代谢紊乱与线粒体功能障碍有关。超过300种致病性mtDNA突变涉及调节OXPHOS和线粒体结构完整性的蛋白质，并且也在具有常染色体遗传的神经退行性疾病中被描述。线粒体可能在衰老相关的神经退行性疾病如帕金森病（PD）中起重要作用。阿尔茨海默病（AD）、亨廷顿病（HD）和肌萎缩侧索硬化（ALS）。在原发性线粒体和神经退行性疾病中，有强有力的证据表明线粒体功能障碍发生早期，并在发病机制中起主要作用。在本综述中，我们讨论了几种线粒体疾病作为神经退行性疾病的模型。(C)2012爱思唯尔有限公司版权所有。
Mitochondria are involved in ATP supply to cells through oxidative phosphorylation (OXPHOS), synthesis of key molecules and response to oxidative stress, as well as in apoptosis. They contain many redox enzymes and naturally occurring inefficiencies of oxidative phosphorylation generate reactive oxygen species (ROS). CNS functions depend heavily on efficient mitochondrial function, since brain tissue has a high energy demand. Mutations in mitochondrial DNA (mtDNA), generation and presence of ROS and environmental factors may contribute to energy failure and lead to neurodegenerative diseases. Many rare metabolic disorders have been associated with mitochondrial dysfunction. More than 300 pathogenic mtDNA mutations involve proteins that regulate OXPHOS and mitochondrial structural integrity, and have also been described in neurodegenerative diseases with autosomal inheritance. Mitochondria may have an important role in ageing-related neurodegenerative disorders like Parkinson's disease (PD). Alzheimer's disease (AD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). In primary mitochondrial and neurodegenerative disorders, there is strong evidence that mitochondrial dysfunction occurs early and has a primary role in pathogenesis. In the present review, we discuss several mitochondrial diseases as models of neurodegeneration. (C) 2012 Elsevier B.V. All rights reserved.