文章基本信息

标题：Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease
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作者：Cynthia A. Massaad ; Taneasha M. Washington ; Robia G. Pautler 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：32
页码：13576-13581
DOI：10.1073/pnas.0902714106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Alzheimer's disease (AD) is a neurodegenerative disease characterized by impaired cognitive function and the deposition of extracellular amyloid plaques and intracellular tangles. Although the proximal cause of AD is not well understood, it is clear that amyloid-{beta} (A{beta}) plays a critical role in AD pathology. Recent studies also implicate mitochondrial abnormalities in AD. We investigated this idea by crossing mice that overexpress mitochondrial superoxide dismutase (SOD-2) with the Tg2576 mouse model of AD that overexpresses the human amyloid precursor protein carrying the Swedish mutation (K670N:M671L). We found that overexpression of SOD-2 decreased hippocampal superoxide, prevented AD-related learning and memory deficits, and reduced A{beta} plaques. Interestingly, SOD-2 overexpression did not affect the absolute levels of A{beta}1-40 and A{beta}1-42, but did significantly reduce the A{beta}1-42 to A{beta}1-40 ratio, thereby shifting the balance toward a less amyloidogenic A{beta} composition. These findings directly link mitochondrial superoxide to AD pathology and demonstrate the beneficial effects of a mitochondrial anti-oxidant enzyme, hence offering significant therapeutic implications for AD.
关键词：antioxidant ; dementia ; mitochondria ; oxidative stress ; reactive oxygen species