Bowling A C, Beal M F
Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114, USA.
Life Sci. 1995;56(14):1151-71. doi: 10.1016/0024-3205(95)00055-b.
Aging is a major risk factor for several common neurodegenerative diseases, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Huntington's disease (HD). Recent studies have implicated mitochondrial dysfunction and oxidative stress in the aging process and also in the pathogenesis of neurodegenerative diseases. In brain and other tissues, aging is associated with progressive impairment of mitochondrial function and increased oxidative damage. In PD, several studies have demonstrated decreased complex I activity, increased oxidative damage, and altered activities of antioxidant defense systems. Some cases of familial ALS are associated with mutations in the gene for Cu, Zn superoxide dismutase (Cu, Zn SOD) and decreased Cu, Zn SOD activity, while in sporadic ALS oxidative damage may be increased. Defects in energy metabolism and increased cortical lactate levels have been detected in HD patients. Studies of AD patients have identified decreased complex IV activity, and some patients with AD and PD have mitochondrial DNA mutations. The age-related onset and progressive course of these neurodegenerative diseases may be due to a cycling process between impaired energy metabolism and oxidative stress.
衰老是几种常见神经退行性疾病的主要风险因素，包括帕金森病（PD）、肌萎缩侧索硬化症（ALS）、阿尔茨海默病（AD）和亨廷顿舞蹈病（HD）。最近的研究表明，线粒体功能障碍和氧化应激与衰老过程以及神经退行性疾病的发病机制有关。在大脑和其他组织中，衰老与线粒体功能的渐进性损害和氧化损伤增加有关。在帕金森病中，多项研究表明复合体I活性降低、氧化损伤增加以及抗氧化防御系统的活性改变。一些家族性肌萎缩侧索硬化症病例与铜锌超氧化物歧化酶（Cu，Zn SOD）基因的突变以及Cu，Zn SOD活性降低有关，而在散发性肌萎缩侧索硬化症中，氧化损伤可能会增加。在亨廷顿舞蹈病患者中检测到能量代谢缺陷和皮质乳酸水平升高。对阿尔茨海默病患者的研究发现复合体IV活性降低，一些阿尔茨海默病和帕金森病患者存在线粒体DNA突变。这些神经退行性疾病与年龄相关的发病和渐进病程可能归因于能量代谢受损和氧化应激之间的循环过程。
