Butterfield D A, Howard B J, LaFontaine M A
Department of Chemistry, Center of Membrane Sciences and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
Curr Med Chem. 2001 Jun;8(7):815-28. doi: 10.2174/0929867013373048.
Oxidative stress in brain is emerging as a potential causal factor in aging and age-related neurodegenerative disorders. Brain tissue from living patients is difficult to acquire; hence, animal models of aging and age-related neurodegenerative disorders, though not perfect models, have provided tissue to study the role of oxidative stress in these disorders. In this review, the central role of oxidative damage in brain in models of accelerated aging (progeria and Werner's syndrome) and the age-related neurodegenerative disorders, Alzheimer's disease and Huntington's disease, will be presented and evaluated. To the extent that the animal models faithfully mirror their respective disorders, and based on the totality of the studies, it is apparent that oxidative stress, the excess of free radicals over the means of scavenging these harmful agents, may play critical roles in the molecular basis of accelerated aging, Alzheimer's disease, and Huntington's disease.
大脑中的氧化应激正逐渐成为衰老及与年龄相关的神经退行性疾病的一个潜在致病因素。获取活体患者的脑组织很困难;因此,衰老及与年龄相关的神经退行性疾病的动物模型,尽管并非完美模型,但已为研究氧化应激在这些疾病中的作用提供了组织样本。在这篇综述中,将呈现并评估氧化损伤在加速衰老模型(早衰症和沃纳综合征)以及与年龄相关的神经退行性疾病——阿尔茨海默病和亨廷顿病——中的核心作用。就动物模型能够如实反映其各自疾病的程度而言,并且基于所有研究的整体情况,很明显氧化应激,即自由基生成超过清除这些有害物质的能力,可能在加速衰老、阿尔茨海默病和亨廷顿病的分子基础中发挥关键作用。