Department of Pharmacology and Clinical Pharmacology, The University of Auckland, New Zealand.
Curr Pharm Des. 2011;17(31):3398-412. doi: 10.2174/138161211798072544.
Epigenetic alterations have been associated with several human diseases including Alzheimer's disease (AD). AD is a complex neurodegenerative disease characterized by a progressive decline in cognitive functions, neuronal cell loss and by the presence of β amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in the cortex. Mutations in specific genes have been identified but can only explain a small percentage of the AD cases. The origins of the sporadic cases of AD are still not known but there is evidence for a role of epigenetics in the etiology of the disease. In this review we focus on discussing the roles of DNA methylation and hydroxymethylation in the development and potential treatment of AD. We discuss papers showing that there are alterations in methylated cytosine (5mC) levels in AD and also highlight the potential role of hydroxylated methylcytosine (5hmC) in the epigenetic regulation of brain gene expression and perhaps in AD. We discuss the potential influence of environmental factors, working through epigenetic mechanisms, on increasing the risk of developing AD and their potential in treating this major neurodegenerative disorder.
表观遗传改变与包括阿尔茨海默病（AD）在内的多种人类疾病有关。AD 是一种复杂的神经退行性疾病，其特征是认知功能逐渐下降，神经元细胞丧失，以及皮质中β淀粉样蛋白（Aβ）斑块和神经原纤维缠结（NFT）的存在。已经确定了特定基因的突变，但只能解释 AD 病例的一小部分。AD 散发性病例的起源仍不清楚，但有证据表明表观遗传在疾病的病因学中起作用。在这篇综述中，我们重点讨论了 DNA 甲基化和羟甲基化在 AD 发展和潜在治疗中的作用。我们讨论了表明 AD 中存在甲基化胞嘧啶（5mC）水平改变的论文，并强调了羟甲基化胞嘧啶（5hmC）在脑基因表达的表观遗传调控中的潜在作用，也许在 AD 中也是如此。我们讨论了环境因素通过表观遗传机制对增加患 AD 风险的潜在影响，以及它们在治疗这种主要神经退行性疾病方面的潜力。
