Atabaki Rabi, Khaleghzadeh-Ahangar Hossein, Esmaeili Nardana, Mohseni-Moghaddam Parvaneh
Rayan Research Center for Neuroscience & Behavior, Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Department of Physiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
Cell Mol Neurobiol. 2023 Apr;43(3):1049-1059. doi: 10.1007/s10571-022-01250-3. Epub 2022 Jul 14.
Epilepsy is one of the most common serious brain diseases worldwide. Programmed cell death (PCD), a cellular self-destruction phenomenon, has been greatly documented in neurodegenerative diseases. Pyroptosis is a well-known pro-inflammatory PCD, and its involvement in epilepsy has been reported in animal models of epilepsy and also epileptic patients. Canonical (caspase-1-dependent) and non-canonical (caspase-1-independent) pathways are two main mechanisms implicated in pyroptotic cell death. Mouse caspase-11 or human analogues caspase-4/5 induce the non-canonical pathway. In both pathways, membrane gasdermin (GSDMD) pores contribute to pro-inflammatory cytokine release and lead to membrane destabilization and cell lysis. IL-1β and IL-18 are pro-inflammatory cytokines that are released following pyroptotic PCD. Brain inflammation increases excitability in the nervous system, promotes seizure activity, and is probably associated with the molecular and synaptic changes involved in epileptogenesis. Pro-inflammatory cytokines affect the glutamate and GABA neurotransmitter release as well as their receptors, thereby resulting in seizure activity. This review is intended to provide an overview of the current published works on pyroptotic cell death in epilepsy. The mechanisms by which pro-inflammatory cytokines, including IL-1β and IL-18 can promote epileptic discharges were also collected. According to this survey, since the involvement of pyroptosis in the development of epilepsy has been established, pyroptosis-targeted therapies may represent a novel anti-epileptogenic strategy.
癫痫是全球最常见的严重脑部疾病之一。程序性细胞死亡（PCD），一种细胞自我毁灭现象，在神经退行性疾病中已有大量记载。细胞焦亡是一种众所周知的促炎性程序性细胞死亡，其在癫痫动物模型以及癫痫患者中均有报道。经典（半胱天冬酶-1依赖性）和非经典（半胱天冬酶-1非依赖性）途径是细胞焦亡性细胞死亡的两种主要机制。小鼠半胱天冬酶-11或人类类似物半胱天冬酶-4/5诱导非经典途径。在这两种途径中，膜孔形成蛋白（GSDMD）孔有助于促炎性细胞因子的释放，并导致膜不稳定和细胞裂解。白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）是细胞焦亡性程序性细胞死亡后释放的促炎性细胞因子。脑部炎症会增加神经系统的兴奋性，促进癫痫发作活动，并且可能与癫痫发生过程中涉及的分子和突触变化有关。促炎性细胞因子会影响谷氨酸和γ-氨基丁酸（GABA）神经递质的释放及其受体，从而导致癫痫发作活动。本综述旨在概述目前已发表的关于癫痫中细胞焦亡性细胞死亡的研究成果。还收集了包括IL-1β和IL-18在内的促炎性细胞因子促进癫痫放电的机制。根据这项调查，由于细胞焦亡在癫痫发展中的作用已得到证实，针对细胞焦亡的治疗可能代表一种新型的抗癫痫发生策略。
