Department of Neuroscience, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Neuroscience, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA/Advanced Science Research Center at the Graduate Center of the City University of New York, New York, NY, USA.
Mult Scler. 2018 Jan;24(1):69-74. doi: 10.1177/1352458517737389.
Multiple sclerosis (MS) is a debilitating neurological disease whose onset and progression are influenced by the interplay of genetic and environmental factors. Epigenetic modifications, which include post-translational modification of the histones and DNA, are considered mediators of gene-environment interactions and a growing body of evidence suggests that they play an important role in MS pathology and could be potential therapeutic targets. Since epigenetic events regulate transcription of different genes in a cell type-specific fashion, we caution on the distinct functional consequences that targeting the same epigenetic modifications might have in distinct cell types. In this review, we primarily focus on the role of histone acetylation and DNA methylation on oligodendrocyte and T-cell function and its potential implications for MS. We find that decreased histone acetylation and increased DNA methylation in oligodendrocyte lineage (OL) cells enhance myelin repair, which is beneficial for MS, while the same epigenetic processes in T cells augment their pro-inflammatory phenotype, which can exacerbate disease severity. In conclusion, epigenetic-based therapies for MS may have great value but only when cellular specificity is taken into consideration.
多发性硬化症(MS)是一种使人衰弱的神经系统疾病,其发病和进展受到遗传和环境因素相互作用的影响。表观遗传修饰,包括组蛋白和 DNA 的翻译后修饰,被认为是基因-环境相互作用的介质,越来越多的证据表明它们在 MS 发病机制中发挥重要作用,并可能成为潜在的治疗靶点。由于表观遗传事件以细胞类型特异性的方式调节不同基因的转录,我们要注意针对相同的表观遗传修饰在不同细胞类型中可能具有不同的功能后果。在这篇综述中,我们主要关注组蛋白乙酰化和 DNA 甲基化对少突胶质细胞和 T 细胞功能的作用及其对 MS 的潜在影响。我们发现,少突胶质细胞谱系(OL)细胞中组蛋白乙酰化减少和 DNA 甲基化增加增强了髓鞘修复,这对 MS 有益,而 T 细胞中相同的表观遗传过程增强了它们的促炎表型,这可能加重疾病的严重程度。总之,基于表观遗传学的 MS 治疗方法可能具有很大的价值,但只有在考虑到细胞特异性时才会如此。