Moreira Paula I, Nunomura Akihiko, Nakamura Masao, Takeda Atsushi, Shenk Justin C, Aliev Gjumrakch, Smith Mark A, Perry George
Center for Neuroscience and Cell Biology, Institute of Physiology-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Free Radic Biol Med. 2008 Apr 15;44(8):1493-505. doi: 10.1016/j.freeradbiomed.2008.01.002. Epub 2008 Jan 18.
Increasing evidence suggests that oxidative stress is intimately associated with Alzheimer disease pathophysiology. Nucleic acids (nuclear DNA, mitochondrial DNA, and RNA) are one of the several cellular macromolecules damaged by reactive oxygen species, particularly the hydroxyl radical. Because neurons are irreplaceable and survive as long as the organism does, they need elaborate defense mechanisms to ensure their longevity. In Alzheimer disease, however, an accumulation of nucleic acid oxidation is observed, indicating an increased level of oxidative stress and/or a decreased capacity to repair the nucleic acid damage. In this review, we present data supporting the notion that mitochondrial and metal abnormalities are key sources of oxidative stress in Alzheimer disease. Furthermore, we outline the mechanisms of nucleic acid oxidation and repair. Finally, evidence showing the occurrence of nucleic acid oxidation in Alzheimer disease will be discussed.
越来越多的证据表明，氧化应激与阿尔茨海默病的病理生理密切相关。核酸（核DNA、线粒体DNA和RNA）是受活性氧特别是羟基自由基损伤的几种细胞大分子之一。由于神经元不可替代且与机体共存，它们需要复杂的防御机制来确保其长寿。然而，在阿尔茨海默病中，观察到核酸氧化的积累，这表明氧化应激水平升高和/或修复核酸损伤的能力下降。在本综述中，我们提供数据支持线粒体和金属异常是阿尔茨海默病氧化应激关键来源的观点。此外，我们概述了核酸氧化和修复的机制。最后，将讨论显示阿尔茨海默病中核酸氧化发生的证据。
