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甲基化在多发性硬化症中的新作用:超越DNA。

Emerging Role for Methylation in Multiple Sclerosis: Beyond DNA.

作者信息

Webb Lindsay M, Guerau-de-Arellano Mireia

机构信息

School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, College of Medicine, Wexner Medical Center, Ohio State University, Columbus, OH 43210, USA; Biomedical Sciences Graduate Program, Ohio State University, Columbus, OH 43210, USA.

School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, College of Medicine, Wexner Medical Center, Ohio State University, Columbus, OH 43210, USA; Department of Microbial Infection and Immunity, Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, Ohio State University, Columbus, OH 43210, USA; Institute of Behavioral Medicine Research, Ohio State University, Columbus, OH 43210, USA.

出版信息

Trends Mol Med. 2017 Jun;23(6):546-562. doi: 10.1016/j.molmed.2017.04.004. Epub 2017 May 4.

Abstract

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The inflammatory and neurodegenerative pathways driving MS are modulated by DNA, lysine, and arginine methylation, as evidenced by studies made possible by novel tools for methylation detection or loss of function. We present evidence that MS is associated with genetic variants and metabolic changes that impact on methylation. Further, we comprehensively review current understanding of how methylation can impact on central nervous system (CNS) resilience and neuroregenerative potential, as well as inflammatory versus regulatory T helper (Th) cell balance. These findings are discussed in the context of therapeutic relevance for MS, with broad implications in other neurologic and immune-mediated diseases.

摘要

多发性硬化症(MS)是一种中枢神经系统的慢性炎症性疾病。驱动MS的炎症和神经退行性通路受到DNA、赖氨酸和精氨酸甲基化的调节,新型甲基化检测工具或功能丧失研究证明了这一点。我们提供的证据表明,MS与影响甲基化的基因变异和代谢变化有关。此外,我们全面回顾了目前对甲基化如何影响中枢神经系统(CNS)弹性和神经再生潜力,以及炎症与调节性T辅助(Th)细胞平衡的理解。这些发现将在MS治疗相关性的背景下进行讨论,对其他神经和免疫介导的疾病具有广泛影响。

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