神经发育和精神障碍的表观遗传学

T. Kubota, Kunio Miyake, T. Hirasawa
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引用次数: 6

摘要

表观遗传机制是胚胎发生和神经细胞分化过程中正常发育所必需的。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至关重要。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。几条线索的证据表明,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节,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分离的可逆机制。此外,最近的研究表明,表观遗传蛋白,如MeCP2,作为“润滑剂”,而不是组成大脑结构的必要部分,在大脑发育的相对较晚的时期起作用。因此,利用这种表观遗传可逆性,纠正异常的表观基因组模式,调控或上调表观遗传分子,将有可能成为治疗由表观遗传异常引起的神经发育和精神障碍的有效方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Epigenetics in Neurodevelopmental and Mental Disorders
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.
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