Department of Chemistry, Aristotle University, Thessaloniki, Greece.
Curr Med Chem. 2011;18(12):1751-6. doi: 10.2174/092986711795496872.
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders affecting elderly people (over 65 years old). Only a small percentage (less than 5%) of the disease is consistent with the Mendelian form of inheritance. The rest, named as Late Onset Alzheimer's Disease (more than 95%), is characterized as a complex multi-factorial disorder, missing familial traits. Although some genes have been implicated in the pathogenesis and the risk of developing sporadic AD, they only account for the minority of LOAD cases. Thus, over the past few years emerging data suggest a potential role of epigenetic mechanisms and chromatin remodeling on neurodegenerative processes leading to dementia. Alterations on the epigenomic machinery cause aberrant DNA methylation and histone acetylation. Therefore, these changes trigger alterations on the transcriptional level of genes involved in the pathogenesis of AD, such as APP. In this review we summarize recent advances on synaptic dysfunction and cognitive decline caused by common epigenetic modifications. We also discuss potential treatment strategies targeting on the epigenetic machinery.
阿尔茨海默病（AD）是最常见的影响老年人（65 岁以上）的神经退行性疾病之一。只有一小部分（小于 5%）的疾病与孟德尔形式的遗传一致。其余的，称为迟发性阿尔茨海默病（超过 95%），其特征为复杂的多因素疾病，缺乏家族特征。尽管一些基因已被牵连到散发性 AD 的发病机制和发病风险中，但它们只占 LOAD 病例的少数。因此，在过去的几年中，新出现的数据表明，表观遗传机制和染色质重塑在导致痴呆的神经退行性过程中可能具有潜在作用。表观基因组机制的改变导致异常的 DNA 甲基化和组蛋白乙酰化。因此，这些变化会引发与 AD 发病机制相关的基因的转录水平发生改变，例如 APP。在这篇综述中，我们总结了常见表观遗传修饰引起的突触功能障碍和认知能力下降的最新进展。我们还讨论了针对表观遗传机制的潜在治疗策略。
