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自闭症中的基因-环境相互作用与表观遗传途径:一碳代谢的重要性。

Gene-environment interactions and epigenetic pathways in autism: the importance of one-carbon metabolism.

作者信息

Schaevitz Laura R, Berger-Sweeney Joanne E

机构信息

School of Arts and Sciences, Tufts University, Medford, Massachusetts 02155, USA.

出版信息

ILAR J. 2012;53(3-4):322-40. doi: 10.1093/ilar.53.3-4.322.

Abstract

Both genetic and epigenetic factors play important roles in the rate and severity of classic autism and autism spectrum disorders (ASDs). This review focuses on DNA methylation as a key epigenetic mechanism in autism. The critical role that one-carbon (C1) metabolism plays in establishing and maintaining DNA methylation patterns makes it a likely candidate pathway to regulate epigenetic processes in ASDs. This review is the first, to our knowledge, to examine how altering C1 metabolic function through genetic and environmental factors (focusing on diet) may lead to aberrant DNA methylation and increase susceptibility to ASDs. Additionally, the critical time windows for sensitivity to genetic and dietary factors both during the development of cortical networks implicated in ASDs and in regard to potential treatments are discussed. One thing is clear, if C1 metabolism plays a critical role in ASDs, it provides a potential avenue for treatment and perhaps, ultimately, prevention.

摘要

遗传因素和表观遗传因素在典型自闭症及自闭症谱系障碍(ASD)的发病率和严重程度方面均发挥着重要作用。本综述聚焦于DNA甲基化,将其作为自闭症中的一种关键表观遗传机制。一碳(C1)代谢在建立和维持DNA甲基化模式中所起的关键作用,使其成为调节ASD表观遗传过程的一个可能候选途径。据我们所知,本综述首次探讨了通过遗传和环境因素(重点是饮食)改变C1代谢功能如何可能导致异常的DNA甲基化并增加患ASD的易感性。此外,还讨论了在与ASD相关的皮质网络发育过程中以及在潜在治疗方面,对遗传和饮食因素敏感的关键时间窗。有一点是明确的,如果C1代谢在ASD中起关键作用,那么它为治疗乃至最终预防提供了一条潜在途径。

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