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认知障碍中的表观遗传失调。

Epigenetic dysregulation in cognitive disorders.

作者信息

Gräff Johannes, Mansuy Isabelle M

机构信息

Brain Research Institute, Medical Faculty of the University of Zürich, Zürich, Switzerland.

出版信息

Eur J Neurosci. 2009 Jul;30(1):1-8. doi: 10.1111/j.1460-9568.2009.06787.x. Epub 2009 Jun 10.

Abstract

Epigenetic mechanisms are not only essential for biological functions requiring stable molecular changes such as the establishment of cell identity and tissue formation, they also constitute dynamic intracellular processes for translating environmental stimuli into modifications in gene expression. Over the past decade it has become increasingly clear that both aspects of epigenetic mechanisms play a pivotal role in complex brain functions. Evidence from patients with neurodegenerative and neurodevelopmental disorders such as Alzheimer's disease and Rett syndrome indicated that epigenetic mechanisms and chromatin remodeling need to be tightly controlled for proper cognitive functions, and their dysregulation can have devastating consequences. However, because they are dynamic, epigenetic mechanisms are also potentially reversible and may provide powerful means for pharmacological intervention. This review outlines major cognitive disorders known to be associated with epigenetic dysregulation, and discusses the potential of 'epigenetic medicine' as a promising cure.

摘要

表观遗传机制不仅对于诸如细胞身份确立和组织形成等需要稳定分子变化的生物学功能至关重要,它们还构成了将环境刺激转化为基因表达修饰的动态细胞内过程。在过去十年中,越来越清楚的是,表观遗传机制的这两个方面在复杂的脑功能中都起着关键作用。来自患有神经退行性和神经发育障碍(如阿尔茨海默病和雷特综合征)患者的证据表明,表观遗传机制和染色质重塑需要受到严格控制以实现适当的认知功能,而它们的失调可能会产生毁灭性后果。然而,由于它们是动态的,表观遗传机制也可能是可逆的,并可能为药物干预提供有力手段。本综述概述了已知与表观遗传失调相关的主要认知障碍,并讨论了“表观遗传医学”作为一种有前景的治疗方法的潜力。

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