Su Yang, Cao Ningrui, Zhang Dingkun, Wang Minjin
Department of Laboratory Medicine, West China Hospital of Sichuan University, China.
West China School of Medicine, Sichuan University, Chengdu, China.
Ageing Res Rev. 2024 Apr;96:102248. doi: 10.1016/j.arr.2024.102248. Epub 2024 Feb 24.
Temporal lobe epilepsy (TLE) is the most common form of epileptic syndrome. It has been established that due to its complex pathogenesis, a considerable proportion of TLE patients often progress to drug-resistant epilepsy. Ferroptosis has emerged as an important neuronal death mechanism in TLE, which is primarily influenced by lipid accumulation and oxidative stress. In previous studies of ferroptosis, more attention has been focused on the impact of changes in the levels of proteins related to the redox equilibrium and signaling pathways on epileptic seizures. However, it is worth noting that the oxidative-reduction changes in different organelles may have different pathophysiological significance in the process of ferroptosis-related diseases. Mitochondria, as a key organelle involved in ferroptosis, its structural damage and functional impairment can lead to energy metabolism disorders and disruption of the excitatory inhibitory balance, significantly increasing the susceptibility to epileptic seizures. Therefore, secondary mitochondrial dysfunction in the process of ferroptosis could play a crucial role in TLE pathogenesis. This review focuses on ferroptosis and mitochondria, discussing the pathogenic role of ferroptosis-related mitochondrial dysfunction in TLE, thus aiming to provide novel insights and potential implications of ferroptosis-related secondary mitochondrial dysfunction in epileptic seizures and to offer new insights for the precise exploration of ferroptosis-related therapeutic targets for TLE patients.
颞叶癫痫（TLE）是最常见的癫痫综合征形式。已经确定，由于其复杂的发病机制，相当一部分TLE患者常进展为药物难治性癫痫。铁死亡已成为TLE中一种重要的神经元死亡机制，其主要受脂质蓄积和氧化应激影响。在以往关于铁死亡的研究中，更多的注意力集中在氧化还原平衡和信号通路相关蛋白质水平变化对癫痫发作的影响上。然而，值得注意的是，不同细胞器中的氧化还原变化在铁死亡相关疾病过程中可能具有不同的病理生理意义。线粒体作为参与铁死亡的关键细胞器，其结构损伤和功能损害可导致能量代谢紊乱以及兴奋性抑制平衡破坏，显著增加癫痫发作的易感性。因此，铁死亡过程中的继发性线粒体功能障碍可能在TLE发病机制中起关键作用。本综述聚焦于铁死亡和线粒体，探讨铁死亡相关线粒体功能障碍在TLE中的致病作用，从而旨在提供铁死亡相关继发性线粒体功能障碍在癫痫发作中的新见解和潜在影响，并为精确探索TLE患者铁死亡相关治疗靶点提供新的思路。
