Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Free Radic Res. 2012 Apr;46(4):565-76. doi: 10.3109/10715762.2011.648188. Epub 2012 Jan 23.
The study of Alzheimer's disease neuropathology has been intimately associated with the field of oxidative stress for nearly 20 years. Indeed, increased markers of oxidative stress have been associated with this neurodegenerative condition, resulting from oxidation of lipids, proteins and nucleic acids. Increased nuclear and mitochondrial DNA oxidation are observed in Alzheimer's disease, stemming from increased reactive oxygen species attack to DNA bases and from the impairment of DNA repair mechanisms. Moreover, mitochondrial DNA is found to be more extensively oxidized than nuclear DNA. This review is intended to summarizes the most important cellular reactive oxygen species producers and how mitochondrial dysfunction, redox-active metals dyshomeostasis and NADPH oxidases contribute to increased oxidative stress in Alzheimer's disease. A summary of the antioxidant system malfunction will also be provided. Moreover, we will highlight the mechanisms of DNA oxidation and repair. Importantly, we will discuss evidence relating the DNA repair machinery and accumulated DNA oxidation with Alzheimer's disease.
阿尔茨海默病神经病理学的研究与氧化应激领域密切相关，已有近 20 年的历史。事实上，氧化应激标志物的增加与这种神经退行性疾病有关，这是由于脂质、蛋白质和核酸的氧化所致。阿尔茨海默病中观察到核和线粒体 DNA 氧化增加，这源自于活性氧对 DNA 碱基的攻击以及 DNA 修复机制的损伤。此外，线粒体 DNA 的氧化程度比核 DNA 更严重。本文旨在总结最重要的细胞活性氧产生者，以及线粒体功能障碍、氧化还原活性金属失衡和 NADPH 氧化酶如何导致阿尔茨海默病中氧化应激的增加。还将提供抗氧化系统功能障碍的总结。此外，我们将重点介绍 DNA 氧化和修复的机制。重要的是，我们将讨论与阿尔茨海默病相关的 DNA 修复机制和积累的 DNA 氧化的证据。
