Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK.
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Neuropathol Appl Neurobiol. 2021 Dec;47(7):897-909. doi: 10.1111/nan.12757. Epub 2021 Aug 5.
Neurodegenerative movement disorders (NMDs) are age-dependent disorders that are characterised by the degeneration and loss of neurons, typically accompanied by pathological accumulation of different protein aggregates in the brain, which lead to motor symptoms. NMDs include Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and Huntington's disease, among others. Epigenetic modifications are responsible for functional gene regulation during development, adult life and ageing and have progressively been implicated in complex diseases such as cancer and more recently in neurodegenerative diseases, such as NMDs. DNA methylation is by far the most widely studied epigenetic modification and consists of the reversible addition of a methyl group to the DNA without changing the DNA sequence. Although this research field is still in its infancy in relation to NMDs, an increasing number of studies point towards a role for DNA methylation in disease processes. This review addresses recent advances in epigenetic and epigenomic research in NMDs, with a focus on human brain DNA methylation studies. We discuss the current understanding of the DNA methylation changes underlying these disorders, the potential for use of these DNA modifications in peripheral tissues as biomarkers in early disease detection, classification and progression as well as a promising role in future disease management and therapy.
神经退行性运动障碍(NMDs)是一种与年龄相关的疾病,其特征是神经元退化和丧失,通常伴随着大脑中不同蛋白质聚集体的病理性积累,从而导致运动症状。NMDs 包括帕金森病、多系统萎缩、进行性核上性麻痹和亨廷顿病等。表观遗传修饰负责发育、成年期和衰老过程中的功能性基因调控,并逐渐涉及癌症等复杂疾病,最近也涉及神经退行性疾病,如 NMDs。迄今为止,DNA 甲基化是研究最广泛的表观遗传修饰之一,它包括在不改变 DNA 序列的情况下可逆地向 DNA 添加一个甲基基团。尽管这个研究领域与 NMDs 相关的研究还处于起步阶段,但越来越多的研究表明 DNA 甲基化在疾病过程中起作用。本文综述了 NMDs 中表观遗传学和表观基因组学研究的最新进展,重点关注人类大脑 DNA 甲基化研究。我们讨论了这些疾病背后的 DNA 甲基化变化的当前理解,以及将这些 DNA 修饰作为早期疾病检测、分类和进展的生物标志物在周围组织中的潜在用途,以及在未来疾病管理和治疗中的有前途的作用。