Novel therapeutic approaches for disease-modification of epileptogenesis for curing epilepsy.
Novel therapeutic approaches for disease-modification of epileptogenesis for curing epilepsy.
复制标题
DOI：
10.1016/j.bbadis.2017.02.003
复制
发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Reddy DS
中科院分区：
文献类型：
--
作者：
Clossen BL;Reddy DS
本文介绍了近年来癫痫发生机制的研究进展和预防癫痫的新的治疗方法，特别强调了癫痫发生机制的药理学基础。在这里，我们评估了1982-2016年癫痫的动物研究和人类临床试验。癫痫由许多触发癫痫发生的神经元因素引起，癫痫发生是大脑从正常生理状态转变为癫痫状态的过程。诱发这些变化的事件可能有不同的起源，包括创伤性脑损伤、脑血管损伤、感染、化学性神经毒性和紧急癫痫发作状况，如癫痫持续状态。预期的是，癫痫发生的分子和系统机制尚未得到很好的定义或理解。到目前为止，还没有批准用于预防癫痫的治疗方法。表观遗传失调、神经炎症和神经变性似乎触发癫痫发生。正在确定能够真正预防高危人群癫痫发展的靶向药物。有希望的药物包括雷帕霉素、考克斯-2抑制剂、TRK抑制剂、表观遗传调节剂、JAK-STAT抑制剂和神经类固醇。最近的证据表明，神经类固醇可能在调节癫痫发生中发挥作用。许多有前途的药物正在研究中，用于预防或改变癫痫发生，以阻止癫痫的发展。一些正在开发的药物似乎是预防癫痫的合理药物，因为它们的目标是最初的触发或相关的信号通路，因为大脑变得越来越容易癫痫发作。对目标有效性和临床调查的进一步研究对于开拓癫痫治疗的新领域至关重要。
This article describes the recent advances in epileptogenesis and novel therapeutic approaches for the prevention of epilepsy, with a special emphasis on the pharmacological basis of disease-modification of epileptogenesis for curing epilepsy. Here we assess animal studies and human clinical trials of epilepsy spanning 1982–2016. Epilepsy arises from a number of neuronal factors that trigger epileptogenesis, which is the process by which a brain shifts from a normal physiologic state to an epileptic condition. The events precipitating these changes can be of diverse origin, including traumatic brain injury, cerebrovascular damage, infections, chemical neurotoxicity, and emergency seizure conditions such as status epilepticus. Expectedly, the molecular and system mechanisms responsible for epileptogenesis are not well defined or understood. To date, there is no approved therapy for the prevention of epilepsy. Epigenetic dysregulation, neuroinflammation, and neurodegeneration appear to trigger epileptogenesis. Targeted drugs are being identified that can truly prevent the development of epilepsy in at-risk people. The promising agents include rapamycin, COX-2 inhibitors, TRK inhibitors, epigenetic modulators, JAK-STAT inhibitors, and neurosteroids. Recent evidence suggests that neurosteroids may play a role in modulating epileptogenesis. A number of promising drugs are under investigation for the prevention or modification of epileptogenesis to halt the development of epilepsy. Some drugs in development appear rational for preventing epilepsy because they target the initial trigger or related signaling pathways as the brain becomes progressively more prone to seizures. Additional research into the target validity and clinical investigation is essential to make new frontiers in curing epilepsy.