Day Jeremy J, Kennedy Andrew J, Sweatt J David
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294; email:
Annu Rev Pharmacol Toxicol. 2015;55:591-611. doi: 10.1146/annurev-pharmtox-010814-124527. Epub 2014 Oct 17.
In this review, we discuss the potential pharmacological targeting of a set of powerful epigenetic mechanisms: DNA methylation control systems in the central nervous system (CNS). Specifically, we focus on the possible use of these targets for novel future treatments for learning and memory disorders. We first describe several unique pharmacological attributes of epigenetic mechanisms, especially DNA cytosine methylation, as potential drug targets. We then present an overview of the existing literature regarding DNA methylation control pathways and enzymes in the nervous system, particularly as related to synaptic function, plasticity, learning and memory. Lastly, we speculate upon potential categories of CNS cognitive disorders that might be amenable to methylomic targeting.
在本综述中，我们讨论了一组强大的表观遗传机制的潜在药理学靶向作用：中枢神经系统（CNS）中的DNA甲基化控制系统。具体而言，我们关注这些靶点在未来用于学习和记忆障碍新治疗方法的可能性。我们首先描述了表观遗传机制，尤其是DNA胞嘧啶甲基化作为潜在药物靶点的几个独特药理学特性。然后，我们概述了关于神经系统中DNA甲基化控制途径和酶的现有文献，特别是与突触功能、可塑性、学习和记忆相关的文献。最后，我们推测了可能适用于甲基组靶向的中枢神经系统认知障碍的潜在类别。
