Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia.
Department of Neuroscience, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, Australia.
J Neurochem. 2019 Dec;151(5):542-557. doi: 10.1111/jnc.14663. Epub 2019 Feb 12.
Epilepsy is a serious neurological condition exhibiting complex pathology and deserving of more serious attention. More than 30% of people with epilepsy are not responsive to more than 20 anti-epileptic drugs currently available, reflecting an unmet clinical need for novel therapeutic strategies. Not much is known about the pathogenesis of epilepsy, but evidence indicates that neuroinflammation might contribute to the onset and progression of epilepsy following acquired brain insults. However, the molecular mechanisms underlying these pathophysiological processes are yet to be fully understood. The emerging research suggests that high-mobility group box protein 1 (HMGB1), a DNA-binding protein that is both actively secreted by inflammatory cells and released by necrotic cells, might contribute to the pathogenesis of epilepsy. HMGB1 as an initiator and amplifier of neuroinflammation, and its activation is implicated in the propagation of seizures in animal models. The current review will highlight the potential role of HMGB1 in the pathogenesis of epilepsy, and implications of HMGB1-targeted therapies against epilepsy. HMGB1 in this context is an emerging concept deserving further exploration. Increased understanding of HMGB1 in seizures and epilepsy will pave the way in designing novel and innovative therapeutic strategies that could modify the disease course or prevent its development.
癫痫是一种严重的神经系统疾病，具有复杂的病理，值得给予更认真的关注。目前有超过 30%的癫痫患者对 20 多种现有抗癫痫药物没有反应，这反映了临床上对新型治疗策略的需求尚未得到满足。对于癫痫的发病机制了解甚少，但有证据表明，神经炎症可能导致获得性脑损伤后癫痫的发作和进展。然而，这些病理生理过程的分子机制尚未完全理解。新出现的研究表明，高迁移率族蛋白 B1（HMGB1）可能与癫痫的发病机制有关。HMGB1 是一种 DNA 结合蛋白，既能被炎症细胞主动分泌，也能由坏死细胞释放，它是神经炎症的启动子和放大器，其激活与动物模型中癫痫发作的传播有关。本综述将重点介绍 HMGB1 在癫痫发病机制中的潜在作用，以及针对癫痫的 HMGB1 靶向治疗的意义。在这种情况下，HMGB1 是一个新兴概念，值得进一步探索。增加对 HMGB1 在癫痫发作和癫痫中的理解，将为设计新型创新治疗策略铺平道路，这些策略可能改变疾病进程或预防其发展。
