Yang Jenq-Lin, Weissman Lior, Bohr Vilhelm A, Mattson Mark P
Laboratory of Molecular Gerontology, National Institute on Aging Intramural Research Program, Baltimore, MD, USA.
DNA Repair (Amst). 2008 Jul 1;7(7):1110-20. doi: 10.1016/j.dnarep.2008.03.012. Epub 2008 May 7.
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.
通过产生三磷酸腺苷（ATP）并调节细胞内钙水平，线粒体对于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损伤会损害神经元中的线粒体能量代谢和离子稳态，从而使它们易发生退化。在所有主要的神经退行性疾病——阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症中，均已记录到线粒体异常。线粒体DNA损伤和功能障碍可能是诸如致病蛋白积累等原发性疾病过程的下游结果。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。针对线粒体调节系统的治疗干预措施在细胞培养和动物模型中已显示出有效性，但其在人类中的疗效仍有待确定。
