1 Evelyn F. McKnight Brain Institute, Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, AL, USA.
2 Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Neuroscientist. 2018 Apr;24(2):186-200. doi: 10.1177/1073858417705840. Epub 2017 May 4.
Epilepsy is a common and devastating neurological disorder characterized by recurrent and unprovoked spontaneous seizures. One leading hypothesis for the development and progression of epilepsy is that large-scale changes in gene transcription and protein expression contribute to aberrant network restructuring and hyperexcitability, resulting in the genesis of repeated seizures. Current research shows that epigenetic mechanisms, including posttranslational alterations to the proteins around which DNA is coiled, chemical modifications to DNA, and the activity of various noncoding RNA molecules exert important influences on these gene networks in experimental epilepsy. Key findings from animal models have been replicated in humans using brain tissue obtained from living patients at the time of neurosurgical resection for pharmacoresistant epilepsy. These findings have spurred efforts to target epigenetic processes to disrupt or modify epilepsy in experimental models with varying degrees of success. In this review, we will (1) summarize the epigenetic mechanisms implicated in epileptogenesis and epilepsy, (2) explore the influence of metabolic factors on epigenetic mechanisms, and (3) assess the potential of using epigenetic markers to support diagnosis and prognosis. Translation of these findings may guide the development of molecular biomarkers and novel therapeutics for prevention or modification of epileptic disorders.
癫痫是一种常见且具有破坏性的神经系统疾病，其特征是反复发作且无诱因的自发性癫痫发作。癫痫发生和发展的一个主要假说是，基因转录和蛋白质表达的大规模变化导致异常的网络重构和过度兴奋，从而导致反复癫痫发作的发生。目前的研究表明，表观遗传机制，包括围绕 DNA 卷曲的蛋白质的翻译后改变、DNA 的化学修饰以及各种非编码 RNA 分子的活性，对实验性癫痫中的这些基因网络产生重要影响。使用从进行抗药性癫痫神经外科切除手术的活体患者的脑组织，在人类中复制了动物模型中的关键发现。这些发现促使人们努力针对表观遗传过程，以在实验模型中破坏或改变癫痫，取得了不同程度的成功。在这篇综述中，我们将：（1）总结参与癫痫发生和癫痫的表观遗传机制；（2）探讨代谢因素对表观遗传机制的影响；（3）评估使用表观遗传标志物来支持诊断和预后的潜力。这些发现的转化可能指导分子生物标志物和新型治疗药物的开发，以预防或改变癫痫性疾病。
