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精神分裂症中的DNA甲基化:表观遗传学研究的进展与挑战

DNA methylation in schizophrenia: progress and challenges of epigenetic studies.

作者信息

Nishioka Masaki, Bundo Miki, Kasai Kiyoto, Iwamoto Kazuya

机构信息

Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 1138655, Japan ; Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 1138655, Japan.

Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 1138655, Japan.

出版信息

Genome Med. 2012 Dec 13;4(12):96. doi: 10.1186/gm397. eCollection 2012.

Abstract

Schizophrenia is a severe psychiatric disease affecting about 1% of the world's population, with significant effects on patients and society. Genetic studies have identified several candidate risk genes or genomic regions for schizophrenia, and epidemiological studies have revealed several environmental risk factors. However, the etiology of schizophrenia still remains largely unknown. Epigenetic mechanisms such as DNA methylation and histone modifications can explain the interaction between genetic and environmental factors at the molecular level, and accumulating evidence suggests that such epigenetic alterations are involved in the pathophysiology of schizophrenia. However, replication studies to validate previous findings and investigations of the causality of epigenetic alterations in schizophrenia are needed. Here, we review epigenetic studies of schizophrenia patients using postmortem brains or peripheral tissues, focusing mainly on DNA methylation. We also highlight the recent progress and challenges in characterizing the potentially complex and dynamic patterns of epigenomic variations. Such studies are expected to contribute to our understanding of schizophrenia etiology and should provide novel opportunities for the development of therapeutic drugs.

摘要

精神分裂症是一种严重的精神疾病,影响着全球约1%的人口,对患者和社会都有重大影响。基因研究已经确定了几个精神分裂症的候选风险基因或基因组区域,流行病学研究也揭示了一些环境风险因素。然而,精神分裂症的病因在很大程度上仍然未知。DNA甲基化和组蛋白修饰等表观遗传机制可以在分子水平上解释遗传和环境因素之间的相互作用,越来越多的证据表明,这种表观遗传改变参与了精神分裂症的病理生理过程。然而,需要进行复制研究来验证先前的发现,并对精神分裂症表观遗传改变的因果关系进行研究。在这里,我们回顾了使用死后大脑或外周组织对精神分裂症患者进行的表观遗传学研究,主要关注DNA甲基化。我们还强调了在表征表观基因组变异潜在复杂和动态模式方面的最新进展和挑战。此类研究有望有助于我们对精神分裂症病因的理解,并应为治疗药物的开发提供新的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9af3/3580436/ddbabe06562c/gm397-1.jpg

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