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自闭症的表观遗传学研究:治疗的新视角。

Epigenetic findings in autism: new perspectives for therapy.

机构信息

Department of Experimental Medicine, Second University of Naples; via S. Maria di Costantinopoli, Napoli 16-80138, Italy.

出版信息

Int J Environ Res Public Health. 2013 Sep 11;10(9):4261-73. doi: 10.3390/ijerph10094261.

Abstract

Autism and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders characterized by dysfunctions in social interactions, communications, restricted interests, and repetitive stereotypic behaviors. Despite extensive genetic and biological research, significant controversy surrounds our understanding of the specific mechanisms of their pathogenesis. However, accumulating evidence points to the involvement of epigenetic modifications as foundational in creating ASD pathophysiology. Epigenetic modifications or the alteration of DNA transcription via variations in DNA methylation and histone modifications but without alterations in the DNA sequence, affect gene regulation. These alterations in gene expression, obtained through DNA methylation and/or histone modifications, result from transcriptional regulatory influences of environmental factors, such as nutritional deficiencies, various toxicants, immunological effects, and pharmaceuticals. As such these effects are epigenetic regulators which determine the final biochemistry and physiology of the individual. In contrast to psychopharmacological interventions, bettering our understanding of how these gene-environmental interactions create autistic symptoms should facilitate the development of therapeutic targeting of gene expression for ASD biomedical care.

摘要

自闭症和自闭症谱系障碍(ASD)是一种复杂的神经发育障碍,其特征是社交互动、沟通、受限兴趣和重复刻板行为方面的功能障碍。尽管进行了广泛的遗传和生物学研究,但我们对其发病机制的具体机制的理解仍存在很大争议。然而,越来越多的证据表明,表观遗传修饰的参与是 ASD 病理生理学的基础。表观遗传修饰或通过 DNA 甲基化和组蛋白修饰改变 DNA 转录,但不改变 DNA 序列,影响基因调控。这些通过 DNA 甲基化和/或组蛋白修饰获得的基因表达变化,是由环境因素的转录调控影响引起的,如营养缺乏、各种毒素、免疫效应和药物。因此,这些影响是表观遗传调节剂,决定个体的最终生化和生理学。与精神药理学干预不同,更好地了解这些基因-环境相互作用如何产生自闭症症状,应该有助于为 ASD 生物医学护理开发针对基因表达的治疗靶向。

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