Center for Genomic Regulation and UPF, Dr Aiguader 88, 08003 Barcelona, Spain.
Clin Genet. 2011 Jul;80(1):1-14. doi: 10.1111/j.1399-0004.2011.01673.x. Epub 2011 May 4.
The risk of developing neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease is influenced by genetic and environmental factors. Environmental events occurring during development or later in life can be related to disease susceptibility. One way by which the environment may exert its effect is through epigenetic modifications, which might affect the functioning of genes. These include nucleosome positioning, post-translational histone modifications, and DNA methylation. In this review we will focus in the potential role of DNA methylation in neurodegenerative disorders and in the approaches to explore such epigenetic changes. Advances in deciphering the role of epigenetic modifications in phenotype are being uncovered for a variety of diseases, including cancer, autoimmune, neurodevelopmental and cognitive disorders. Epigenetic modifications are now being also associated with cardiovascular and metabolic traits, and they are expected to be especially involved in learning and memory processes, as well as in neurodegenerative disease. The study of the role of methylation and other epigenetic modifications in disease development will provide new insights in the etiopathogenesis of neurodegenerative disorders, and should hopefully shape new avenues in the development of therapeutic strategies.
发生在发育过程中或生命后期的环境事件可能与疾病易感性有关。环境可能通过影响基因功能的表观遗传修饰来发挥其作用。这些包括核小体定位、组蛋白翻译后修饰和 DNA 甲基化。在这篇综述中，我们将重点关注 DNA 甲基化在神经退行性疾病中的潜在作用，以及探索这种表观遗传变化的方法。在包括癌症、自身免疫、神经发育和认知障碍在内的多种疾病中，人们正在揭示表观遗传修饰在表型中的作用的新进展。表观遗传修饰现在也与心血管和代谢特征有关，预计它们将特别参与学习和记忆过程以及神经退行性疾病。研究甲基化和其他表观遗传修饰在疾病发展中的作用将为神经退行性疾病的病因发病机制提供新的见解，并有望为治疗策略的制定开辟新的途径。
