神经轴突蛋白-1在癫痫中的作用机制研究进展

Research Progress on the Mechanisms of Neurexin-1 in Epilepsy

摘要: 癫痫，特别是药物难治性癫痫，是神经系统的重大挑战，其发病机制复杂，仍有待深入阐明。近年来，遗传因素在癫痫中的作用日益受到重视。神经轴突蛋白-1 (NRXN1)基因编码一种关键的突触前细胞粘附分子，通过与其突触后配体(如神经配蛋白，Neuroligin)结合，在突触的形成、维持和功能调控中扮演核心角色。NRXN1的遗传变异已被证实与自闭症谱系障碍、精神分裂症、智力障碍等多种神经精神疾病密切相关，而这些疾病常与癫痫共病，提示NRXN1可能是连接这些疾病的分子桥梁之一。本文旨在综述NRXN1的生物学功能、其在神经系统疾病中的作用，并重点探讨NRXN1表达异常或功能缺失通过影响突触可塑性、扰乱神经环路兴奋/抑制(E/I)平衡，进而参与癫痫发病机制的最新研究进展。对NRXN1的深入研究，有望为揭示癫痫，尤其是难治性癫痫的病因提供新视角，并为开发新的治疗策略提供潜在靶点。

Abstract: Epilepsy, particularly drug-resistant epilepsy, poses a significant challenge to the nervous system. Its pathogenesis is complex and remains to be fully elucidated. In recent years, genetic factors have received increasing attention in epilepsy research. The Neurexin-1 (NRXN1) gene encodes a critical presynaptic cell adhesion molecule that interacts with its postsynaptic ligands, such as Neuroligin, playing a central role in synapse formation, maintenance, and functional regulation. Genetic variations in NRXN1 have been closely associated with various neuropsychiatric disorders, including autism spectrum disorder, schizophrenia, and intellectual disability. These disorders often co-occur with epilepsy, suggesting that NRXN1 may serve as a molecular bridge connecting these conditions. This review aims to summarize the biological functions of NRXN1, its role in nervous system diseases, and, in particular, to discuss the latest research progress on how abnormal expression or functional loss of NRXN1 may contribute to epilepsy pathogenesis by affecting synaptic plasticity and disrupting the excitatory/inhibitory (E/I) balance of neural circuits. In-depth study of NRXN1 is expected to provide new insights into the etiology of epilepsy, especially drug-resistant epilepsy, and offer potential targets for developing novel therapeutic strategies.