Olanow C W, Arendash G W
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029.
Curr Opin Neurol. 1994 Dec;7(6):548-58. doi: 10.1097/00019052-199412000-00013.
Substantial evidence has accumulated implicating metals and free radicals in the pathogenesis of the major neurodegenerative disorders (Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis). Metal-induced oxidant stress can damage critical biological molecules and initiate a cascade of events including mitochondrial dysfunction, excitotoxicity, and a rise in cytosolic free calcium, leading to cell death. In Parkinson's disease and Alzheimer's disease there is evidence of oxidative stress in affected brain regions, as indicated by increased metal accumulation (which promotes free radical formation), decreased antioxidant levels (which protect against free radical formation), and oxidative damage. Recently, studies of the familial form of amyotrophic lateral sclerosis have detected mutations in the gene that encodes superoxide dismutase, which is one of the body's primary oxidant defense mechanisms. Mice that are transfected with the human mutant superoxide dismutase gene develop an amyotrophic lateral sclerosis syndrome. These studies demonstrate that oxidant stress can initiate the development of a chronic progressive neurodegenerative disorder.
大量证据表明，金属和自由基与主要神经退行性疾病（帕金森病、阿尔茨海默病和肌萎缩侧索硬化症）的发病机制有关。金属诱导的氧化应激会损害关键生物分子，并引发一系列事件，包括线粒体功能障碍、兴奋性毒性和细胞溶质游离钙升高，导致细胞死亡。在帕金森病和阿尔茨海默病中，受影响脑区存在氧化应激的证据，表现为金属积累增加（促进自由基形成）、抗氧化剂水平降低（防止自由基形成）和氧化损伤。最近，对家族性肌萎缩侧索硬化症的研究发现，编码超氧化物歧化酶的基因突变，超氧化物歧化酶是人体主要的氧化防御机制之一。转染了人类突变超氧化物歧化酶基因的小鼠会出现肌萎缩侧索硬化症综合征。这些研究表明，氧化应激可引发慢性进行性神经退行性疾病的发展。
