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不利环境对神经退行性疾病的表观遗传编程。

Epigenetic programming of neurodegenerative diseases by an adverse environment.

机构信息

Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.

出版信息

Brain Res. 2012 Mar 20;1444:96-111. doi: 10.1016/j.brainres.2012.01.038. Epub 2012 Jan 24.

Abstract

Experience and environment can critically influence the risk and progression of neurodegenerative disorders. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications, readily respond to experience and environmental factors. Here we propose that epigenetic regulation of gene expression and environmental modulation thereof may play a key role in the onset and course of common neurological conditions, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. For example, epigenetic mechanisms may mediate long-term responses to adverse experience, such as stress, to affect disease susceptibility and the course of neurodegenerative events. This review introduces the epigenetic components and their possible role in mediating neuropathological processes in response to stress. We argue that epigenetic modifications will affect neurodegenerative events through altered gene function. The study of epigenetic states in neurodegenerative diseases presents an opportunity to gain new insights into risk factors and pathogenic mechanisms. Moreover, research into epigenetic regulation of disease may revolutionize health care by opening new avenues of personalized, preventive and curative medicine.

摘要

经验和环境会对神经退行性疾病的风险和进展产生重大影响。表观遗传机制,如 miRNA 表达、DNA 甲基化和组蛋白修饰,能迅速对经验和环境因素做出反应。在这里,我们提出基因表达的表观遗传调控及其对环境的调节可能在常见神经疾病(包括阿尔茨海默病、帕金森病、亨廷顿病和多发性硬化症)的发病和病程中起关键作用。例如,表观遗传机制可能介导对压力等不良经历的长期反应,从而影响疾病易感性和神经退行性事件的进程。这篇综述介绍了表观遗传成分及其在介导应激反应中的神经病理过程中的可能作用。我们认为,表观遗传修饰将通过改变基因功能来影响神经退行性事件。对神经退行性疾病中表观遗传状态的研究为深入了解风险因素和发病机制提供了新的视角。此外,对疾病的表观遗传调控的研究通过开辟个性化、预防性和治疗性医学的新途径,可能彻底改变医疗保健。

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