Girona Neuroimmunology and Multiple Sclerosis Unit (UNIEM), Dr. Josep Trueta University Hospital and Girona Biomedical Research Institute (IDIBGI), Girona, Spain.
J Neuroinflammation. 2020 Jan 14;17(1):21. doi: 10.1186/s12974-019-1667-1.
Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system characterised by incoordination, sensory loss, weakness, changes in bladder capacity and bowel function, fatigue and cognitive impairment, creating a significant socioeconomic burden. The pathogenesis of MS involves both genetic susceptibility and exposure to distinct environmental risk factors. The gene x environment interaction is regulated by epigenetic mechanisms. Epigenetics refers to a complex system that modifies gene expression without altering the DNA sequence. The most studied epigenetic mechanism is DNA methylation. This epigenetic mark participates in distinct MS pathophysiological processes, including blood-brain barrier breakdown, inflammatory response, demyelination, remyelination failure and neurodegeneration. In this study, we also accurately summarised a list of environmental factors involved in the MS pathogenesis and its clinical course. A literature search was conducted using MEDLINE through PubMED and Scopus. In conclusion, an exhaustive study of DNA methylation might contribute towards new pharmacological interventions in MS by use of epigenetic drugs.
多发性硬化症(MS)是一种中枢神经系统的自身免疫性脱髓鞘疾病,其特征是协调障碍、感觉丧失、虚弱、膀胱容量和肠道功能改变、疲劳和认知障碍,造成重大的社会经济负担。MS 的发病机制涉及遗传易感性和暴露于特定环境风险因素。基因与环境的相互作用受表观遗传机制的调节。表观遗传学是指一种复杂的系统,它可以在不改变 DNA 序列的情况下调节基因表达。研究最多的表观遗传机制是 DNA 甲基化。这种表观遗传标记参与了 MS 的多个病理生理过程,包括血脑屏障破坏、炎症反应、脱髓鞘、髓鞘再生失败和神经退行性变。在这项研究中,我们还准确地总结了与 MS 发病机制及其临床过程相关的一系列环境因素。通过 MEDLINE 数据库在 PubMED 和 Scopus 上进行了文献检索。总之,对 DNA 甲基化的详尽研究可能有助于通过使用表观遗传药物为 MS 提供新的药物干预。