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本文引用的文献

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Efficient Remyelination Requires DNA Methylation.高效的髓鞘再生需要 DNA 甲基化。
eNeuro. 2017 Mar 30;4(2). doi: 10.1523/ENEURO.0336-16.2017. eCollection 2017 Mar-Apr.
2
Whole-Genome DNA Methylation Analysis of Peripheral Blood Mononuclear Cells in Multiple Sclerosis Patients with Different Disease Courses.不同病程多发性硬化症患者外周血单个核细胞的全基因组DNA甲基化分析
Acta Naturae. 2016 Jul-Sep;8(3):103-110.
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Functional Characterization of DNA Methylation in the Oligodendrocyte Lineage.少突胶质细胞谱系中DNA甲基化的功能特征
Cell Rep. 2016 Apr 26;15(4):748-760. doi: 10.1016/j.celrep.2016.03.060. Epub 2016 Apr 14.
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Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients.对多发性硬化症患者CD8 + T细胞进行全基因组DNA甲基化分析,结果显示其表观遗传特征与CD4 + T细胞不同。
Clin Epigenetics. 2015 Nov 5;7:118. doi: 10.1186/s13148-015-0152-7. eCollection 2015.
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Bromodomains: Translating the words of lysine acetylation into myelin injury and repair.溴结构域:将赖氨酸乙酰化的信号转化为髓鞘损伤与修复机制
Neurosci Lett. 2016 Jun 20;625:4-10. doi: 10.1016/j.neulet.2015.10.015. Epub 2015 Oct 22.
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Genome-wide DNA methylation profiles indicate CD8+ T cell hypermethylation in multiple sclerosis.全基因组DNA甲基化谱表明多发性硬化症中CD8 + T细胞存在高甲基化。
PLoS One. 2015 Mar 3;10(3):e0117403. doi: 10.1371/journal.pone.0117403. eCollection 2015.
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5-Hydroxymethylcytosine: a stable or transient DNA modification?5-羟甲基胞嘧啶:一种稳定的还是短暂的DNA修饰?
Genomics. 2014 Nov;104(5):314-23. doi: 10.1016/j.ygeno.2014.08.015. Epub 2014 Aug 30.
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Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression.基因转录的选择性化学调控有利于少突胶质细胞谱系进展。
Chem Biol. 2014 Jul 17;21(7):841-854. doi: 10.1016/j.chembiol.2014.05.009. Epub 2014 Jun 19.
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Low-dose 5-aza-2'-deoxycytidine pretreatment inhibits experimental autoimmune encephalomyelitis by induction of regulatory T cells.低剂量5-氮杂-2'-脱氧胞苷预处理通过诱导调节性T细胞抑制实验性自身免疫性脑脊髓炎。
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10
Hypomethylating agent 5-aza-2'-deoxycytidine (DAC) ameliorates multiple sclerosis in mouse models.低甲基化剂 5-氮杂-2'-脱氧胞苷(DAC)改善了多发性硬化症的小鼠模型。
J Cell Physiol. 2014 Dec;229(12):1918-25. doi: 10.1002/jcp.24641.

多发性硬化症患者脑和免疫细胞中的表观遗传修饰。

Epigenetic modifications in brain and immune cells of multiple sclerosis patients.

机构信息

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.

出版信息

Mult Scler. 2018 Jan;24(1):69-74. doi: 10.1177/1352458517737389.

DOI:10.1177/1352458517737389
PMID:29307300
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5761344/
Abstract

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.

摘要

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。