Maqbool Mudasir, Khan Yumna, Arab Mohammed M, Alshammari Saud O, Hussain Md Sadique, Almufarriji Fawaz M
Department of Pharmacology, Government Medical College, Baramulla, Jammu and Kashmir 193103, India.
Institute of Biotechnology and Genetic Engineering (Health Division), The University of Agriculture, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan.
EXCLI J. 2025 May 30;24:578-611. doi: 10.17179/2025-8359. eCollection 2025.
Epilepsy is a highly complex and global neurological disorder, for which available treatments only inadequately control the disease in many patients. Recent advances in molecular research have identified N6-methyladenosine (m6A) RNA modifications as key regulators of neuronal processes that underpin the pathophysiology of epilepsy. This review critically discusses the emerging significance of m6A modifications in epilepsy, focusing on dynamic regulations of m6A "writers," "erasers," and "readers" for modulating gene expression, neuronal excitability, and synaptic plasticity in epilepsy. Dysregulation of m6A machinery promotes epilepsy by exacerbating oxidative stress, mitochondrial dysfunction, and neuronal damage. We also discuss the prognostic significance of m6A alterations as a potential biomarker in epilepsy diagnosis and disease progression, along with advanced therapeutic strategies against m6A, including small molecules, RNA editing technologies, and precision medicine. This review highlights the transformational significance of m6A modulation in epilepsy therapy and opens new avenues for personalized therapeutic strategies that may revolutionize the field of drug-resistant epilepsy and improve the prognosis for patients. See also the graphical abstract(Fig. 1).
癫痫是一种高度复杂的全球性神经系统疾病，目前的治疗方法在许多患者中只能对该疾病进行不充分的控制。分子研究的最新进展已确定N6-甲基腺苷（m6A）RNA修饰是神经元过程的关键调节因子，这些过程是癫痫病理生理学的基础。本综述批判性地讨论了m6A修饰在癫痫中日益凸显的重要性，重点关注m6A“书写器”“擦除器”和“读取器”的动态调节，以调节癫痫中的基因表达、神经元兴奋性和突触可塑性。m6A机制的失调通过加剧氧化应激、线粒体功能障碍和神经元损伤来促进癫痫。我们还讨论了m6A改变作为癫痫诊断和疾病进展中潜在生物标志物的预后意义，以及针对m6A的先进治疗策略，包括小分子、RNA编辑技术和精准医学。本综述强调了m6A调节在癫痫治疗中的变革性意义，并为个性化治疗策略开辟了新途径这可能会彻底改变耐药性癫痫领域并改善患者的预后。另见图1的图形摘要。
