Gross Christina, McGann Amanda M, Tiwari Durgesh
Division of Neurology, Cincinnati Children's Hospital Medical Center, OH, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, OH, USA.
Epilepsy Curr. 2025 Aug 11:15357597251366441. doi: 10.1177/15357597251366441.
Recurrent spontaneous seizures in epilepsy cause a myriad of structural, circuit-related, and molecular modifications in the brain. The multifaceted molecular changes suggest that wide-reaching epigenetic mechanisms are altered in epilepsy. Indeed, it has been known for more than 15 years that a class of epigenetic regulators called microRNAs-short, noncoding RNAs that control the translation and stability of sometimes hundreds of mRNA targets-are dysregulated after seizures and in epilepsy in human patients and rodent models. Epilepsy-associated microRNAs regulate many different molecular contributors to epilepsy, including ion channels, neuroinflammatory modulators, and proteins critical for neuronal and synaptic structure. In recent years, it has become clear that microRNAs are important at every phase of epilepsy-from the onset of the first seizure to the latent phase and chronic epilepsy. In line with these findings, manipulation of a subset of microRNAs has been shown to alter seizure susceptibility, reduce epileptogenesis, and/or decrease the frequency of spontaneous recurrent seizures in animal models of epilepsy. These studies illustrate the promise of microRNAs as future therapeutic targets in epilepsy and show that specific microRNAs play different regulatory roles depending on the phase and type of epilepsy. In this concise review, we summarize recent findings of microRNAs in epilepsy, emphasizing novel approaches that advance the field. We discuss the insight on underlying mechanisms and disease etiology that can be drawn from these studies and highlight the importance of timing when developing microRNA-based therapeutic strategies.
癫痫中的复发性自发性癫痫发作会在大脑中引发无数的结构、回路相关和分子改变。多方面的分子变化表明，广泛的表观遗传机制在癫痫中发生了改变。事实上，15年多来人们已经知道，一类名为微小RNA的表观遗传调节因子——短的非编码RNA，可控制有时数百个mRNA靶标的翻译和稳定性——在癫痫发作后以及人类患者和啮齿动物模型的癫痫中失调。与癫痫相关的微小RNA调节许多不同的癫痫分子因素，包括离子通道、神经炎症调节因子以及对神经元和突触结构至关重要的蛋白质。近年来，越来越清楚的是，微小RNA在癫痫的每个阶段都很重要——从首次发作的开始到潜伏期和慢性癫痫。与这些发现一致，在癫痫动物模型中，对一部分微小RNA的操纵已被证明可改变癫痫易感性、减少癫痫发生和/或降低复发性自发性癫痫发作的频率。这些研究说明了微小RNA作为癫痫未来治疗靶点的前景，并表明特定的微小RNA根据癫痫的阶段和类型发挥不同的调节作用。在这篇简要综述中，我们总结了微小RNA在癫痫方面的最新发现，强调推动该领域发展的新方法。我们讨论了可以从这些研究中得出的关于潜在机制和疾病病因的见解，并强调了在制定基于微小RNA的治疗策略时时间选择的重要性。
