Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment.
Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment.
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DOI：
10.1016/s1474-4422(12)70309-5
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Casaccia P
中科院分区：
文献类型：
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作者：
Huynh JL;Casaccia P
研究多发性硬化症的临床神经学家和科学家面临着关于流行病学数据与全基因组关联研究和患者临床管理整合的开放性问题。越来越明显的是，环境影响和个体遗传易感性的相互作用调节疾病的表现和治疗反应。环境信号转化为基因表达变化的分子机制包括DNA甲基化、核小体组蛋白的翻译后修饰和非编码RNA。这些机制由组织选择性和细胞类型特异性的专门酶家族调节。多发性硬化症发病机制的模型应该整合与遗传易感性相关的潜在风险，以及免疫系统和大脑中响应衰老和环境刺激而发生的细胞类型特异性表观遗传变化。
Clinical neurologists and scientists who study multiple sclerosis face open questions regarding the integration of epidemiological data with genome-wide association studies and clinical management of patients. It is becoming evident that the interplay of environmental influences and individual genetic susceptibility modulates disease presentation and therapeutic responsiveness. The molecular mechanisms through which environmental signals are translated into changes in gene expression include DNA methylation, post-translational modification of nucleosomal histones, and non-coding RNAs. These mechanisms are regulated by families of specialised enzymes that are tissue selective and cell-type specific. A model of multiple sclerosis pathogenesis should integrate underlying risk related to genetic susceptibility with cell-type specific epigenetic changes occurring in the immune system and in the brain in response to ageing and environmental stimuli.