Simonian N A, Coyle J T
Department of Neurology, Massachusetts General Hospital, Boston, USA.
Annu Rev Pharmacol Toxicol. 1996;36:83-106. doi: 10.1146/annurev.pa.36.040196.000503.
Oxidative stress refers to the cytopathologic consequences of a mismatch between the production of free radicals and the ability of the cell to defend against them. Growing data from experimental models and human brain studies suggest oxidative stress may play an important role in neuronal degeneration in diseases such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Mitochondrial oxidative metabolism, nitric oxide, phospholipid metabolism, and proteolytic pathways are potential sources of intracellular free radicals. Alterations in free radical defense systems may also contribute to oxidative stress. A net increase in reactive oxygen species can produce damage to lipids, proteins, and DNA and induce necrosis or apoptosis. Elucidating the pathways important in the production of and defense from free radicals may be important in devising new pharmacologic strategies to slow or halt neuronal degeneration.
氧化应激是指自由基产生与细胞抵御自由基能力之间不匹配所导致的细胞病理后果。来自实验模型和人脑研究的越来越多的数据表明，氧化应激可能在帕金森病、阿尔茨海默病和肌萎缩侧索硬化症等疾病的神经元变性中起重要作用。线粒体氧化代谢、一氧化氮、磷脂代谢和蛋白水解途径是细胞内自由基的潜在来源。自由基防御系统的改变也可能导致氧化应激。活性氧的净增加会对脂质、蛋白质和DNA造成损伤，并诱导坏死或凋亡。阐明自由基产生和防御过程中的重要途径，对于设计新的药理策略以减缓或阻止神经元变性可能具有重要意义。
