Acquired and genetic forms of epilepsy are associated with dysregulation of gene expression within the brain. Identifying mechanisms controlling gene expression may provide novel opportunities for the development of disease-modifying therapies. Epigenetic processes influence the medium-to long-term readability and accessibility of the genome to transcription. The mediators include biochemical modifications to DNA and the histones around which DNA is wrapped, as well as non-coding RNAs. Here, the main epigenetic processes are briefly reviewed. Examples are provided of altered epigenetic processes and mutations in genes with epigenetic functions in experimental models and human epilepsy. The outcome of recent studies manipulating epigenetics to protect the brain or reduce seizures in preclinical models is considered, with specific focus on RNA therapies. Last, future applications of epigenetics research are appraised, including opportunities to map and change epigenetic marks and the prospects for therapies based on manipulation of epigenetics and noncoding RNAs. In summary, epigenetics and noncoding RNAs are important mechanisms and targets to modulate brain excitability which together provides novel insight into patho-mechanisms, biomarkers and novel therapies for epilepsy.

中文翻译：

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表观遗传学和非编码 RNA：最近的发展和未来的治疗机会

获得性和遗传形式的癫痫与大脑内基因表达的失调有关。确定控制基因表达的机制可能为疾病修饰疗法的发展提供新的机会。表观遗传过程影响基因组转录的中长期可读性和可访问性。介质包括对 DNA 的生化修饰和包裹 DNA 的组蛋白，以及非编码 RNA。在这里，简要回顾了主要的表观遗传过程。提供了在实验模型和人类癫痫中具有表观遗传功能的基因中改变的表观遗传过程和突变的例子。最近的研究结果考虑了在临床前模型中操纵表观遗传学以保护大脑或减少癫痫发作，特别关注 RNA 疗法。最后，评估了表观遗传学研究的未来应用，包括绘制和改变表观遗传标记的机会以及基于表观遗传学和非编码 RNA 操作的治疗前景。总之，表观遗传学和非编码 RNA 是调节大脑兴奋性的重要机制和靶点，它们共同为癫痫的病理机制、生物标志物和新疗法提供了新的见解。