The role for oxidative stress in aberrant DNA methylation in Alzheimer's disease.
The role for oxidative stress in aberrant DNA methylation in Alzheimer's disease.
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DOI：
10.2174/156720512803569000
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发表时间：
2012-10
影响因子：
2.1
通讯作者：
J. Fleming;C. Phiel;A. Toland
中科院分区：
文献类型：
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作者：
J. Fleming;C. Phiel;A. Toland
阿尔茨海默病（AD）是一种常见的、进行性的神经退行性疾病，目前尚无有效的治疗方法。AD的病因是异质性的，淀粉样蛋白-β斑块、神经元缠结、氧化应激和异常DNA甲基化均涉及疾病发病机制。DNA甲基化是一个公认的调节基因表达的过程，并已被发现调节越来越多的参与AD发展和进展的重要基因。此外，一碳代谢异常是AD患者中的常见发现，个体表现出低S-腺苷甲硫氨酸和高同型半胱氨酸水平以及低叶酸和维生素B。氧化应激被认为是AD发病机制中最早的事件之一，并且被认为在很大程度上促成神经元细胞死亡。新出现的证据表明氧化应激和DNA甲基化之间存在相互作用;然而，其机制仍不清楚。本文综述了已知的和潜在的基因参与AD的DNA甲基化和氧化应激的调控。我们还强调了通过几种机制以及对疾病理解和治疗发展的影响，氧化损伤在AD患者中促进DNA低甲基化的作用的证据。
Alzheimer's disease (AD) is a common, progressive neurodegenerative disorder without highly effective therapies. The etiology of AD is heterogeneous with amyloid-beta plaques, neurofibrillary tangles, oxidative stress, and aberrant DNA methylation all implicated in the disease pathogenesis. DNA methylation is a well-established process for regulating gene expression and has been found to regulate a growing number of important genes involved in AD development and progression. Additionally, aberrations in one-carbon metabolism are a common finding in AD patients with individuals exhibiting low S-adenosylmethionine and high homocysteine levels as well as low folate and vitamin B. Oxidative stress is considered one of the earliest events in AD pathogenesis and is thought to contribute largely to neuronal cell death. Emerging evidence suggests an interaction exists between oxidative stress and DNA methylation; however, the mechanism(s) remain unclear. This review summarizes known and potential genes implicated in AD that are regulated by DNA methylation and oxidative stress. We also highlight the evidence for the role of oxidative damage contributing to DNA hypomethylation in AD patients through several mechanisms as well as implications for disease understanding and therapeutic development.