Epigenetics in Neurodevelopmental and Mental Disorders
Epigenetics in Neurodevelopmental and Mental Disorders
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DOI：
10.1159/000354718
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发表时间：
2013-08
期刊：
影响因子：
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通讯作者：
T. Kubota;Kunio Miyake;T. Hirasawa
中科院分区：
文献类型：
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作者：
T. Kubota;Kunio Miyake;T. Hirasawa
表观遗传机制对于胚胎发生期间的正常发育和神经细胞的分化是必不可少的。因此，精确理解表观遗传机制，包括DNA甲基化和组蛋白修饰，对于阐明神经发育障碍的致病途径非常重要。这些包括由基因组印记失败、X染色体失活和与表观遗传基因调控相关的蛋白质突变引起的各种先天性疾病。一些证据表明，各种环境因素，包括营养不足，药物和精神压力，可以改变大脑中的表观遗传基因调控，这可能导致自闭症和成人精神障碍。然而，表观遗传机制是基于修饰因子在DNA和组蛋白上的附着和脱离的可逆机制。此外，最近的研究表明，表观遗传蛋白质，如MeCP 2，作为“润滑剂”，而不是构成大脑结构的重要部分，它在大脑发育的相对后期起作用。因此，利用这种表观遗传可逆性，校正异常表观基因组模式和施用或上调表观遗传分子将可能是治疗由表观遗传异常引起的神经发育和精神障碍的有用疗法。
Epigenetic mechanisms are essential for normal development during embryogenesis and for differentiation of neural cells. Thus, precise understanding of epigenetic mechanisms, including DNA methylation and histone modification, is important to elucidate the pathogenic pathways in neurodevelopmental disorders. These include various congenital disorders caused by failures of genomic imprinting, X chromosome inactivation, and mutations of the proteins associated with epigenetic gene regulation. Several lines of evidence have suggested that various environmental factors, including insufficient nutrition, drugs, and mental stress, can alter epigenetic gene regulation in the brain, which potentially cause autism and adult mental disorders. However, epigenetic mechanisms are reversible mechanisms based on the attachment and detachment of modification factors onto DNA and histone proteins. Furthermore, recent studies indicate that epigenetic proteins, such as MeCP2, act as ‘lubricants' rather than essential parts that make up the brain structure, which works at a relatively later period of brain development. Therefore, making use of this epigenetic reversibility, the correction of abnormal epigenomic patterns and the administration or upregulation of epigenetic molecules will potentially be useful therapies for neurodevelopmental and mental disorders caused by epigenetic abnormalities.