摘要
By producing ATP and regulating intracellular calcium levels, mitochondria are vital for the function and survival of neurons. Oxidative stress and damage to mitochondrial DNA during the aging process can impair mitochondrial energy metabolism and ion homeostasis in neurons, thereby rendering them vulnerable to degeneration. Mitochondrial abnormalities have been documented in all of the major neurodegenerative disorders—Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis. Mitochondrial DNA damage and dysfunction may be downstream of primary disease processes such as accumulation of pathogenic proteins. However, recent experimental evidence demonstrates that mitochondrial DNA damage responses play important roles in aging and in the pathogenesis of neurodegenerative diseases. Therapeutic interventions that target mitochondrial regulatory systems have been shown effective in cell culture and animal models, but their efficacy in humans remains to be established.
摘要译文
通过产生ATP和调节细胞内钙水平，线粒体对神经元的功能和存活至关重要。衰老过程中的氧化应激和线粒体DNA的损伤可以损害神经元中的线粒体能量代谢和离子稳态，从而使它们易于变性。所有主要的神经退行性疾病 - 阿尔茨海默氏症，帕金森氏症和亨廷顿舞蹈病以及肌萎缩侧索硬化都有线粒体异常。线粒体DNA损伤和功能障碍可能是原发疾病过程的下游，例如致病蛋白的积累。然而，最近的实验证据表明，线粒体DNA损伤反应在衰老和神经退行性疾病的发病机制中起重要作用。靶向线粒体调节系统的治疗干预已经在细胞培养和动物模型中显示出有效性，但它们在人体中的功效仍有待确定。
Jenq-LinYang[a][b];LiorWeissman[a];Vilhelm A.Bohr[a];Mark P.Mattson[b];. Mitochondrial DNA damage and repair in neurodegenerative disorders[J]. DNA Repair, 2008,7(7): 1110-1120