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癫痫研究和抗癫痫药物开发的新进展:迈向精确的电路治疗。

An update for epilepsy research and antiepileptic drug development: Toward precise circuit therapy.

机构信息

Institute of Pharmacology and Toxicology, Department of Pharmacology, NHC and CAMS Key Laboratory of Medical Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Institute of Pharmacology and Toxicology, Department of Pharmacology, NHC and CAMS Key Laboratory of Medical Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

出版信息

Pharmacol Ther. 2019 Sep;201:77-93. doi: 10.1016/j.pharmthera.2019.05.010. Epub 2019 May 23.

Abstract

Epilepsy involves neuronal dysfunction at molecular, cellular, and circuit levels. The understanding of the mechanism of the epilepsies has advanced greatly in the last three decades, especially in terms of their cellular and molecular basis. However, despite the availability of ~30 anti-epileptic drugs (AEDs) with diverse molecular targets, there are still many challenges (e.g. drug resistance, side effects) in pharmacological treatment of epilepsies today. Because molecular mechanisms are integrated at the level of neuronal circuits, we suggest a shift in epilepsy treatment and research strategies from the "molecular" level to the "circuit" level. Recent technological advances have facilitated circuit mechanistic discovery at each level and have paved the way for many opportunities of novel therapeutic strategies and AED development toward precise circuit therapy.

摘要

癫痫涉及分子、细胞和电路水平的神经元功能障碍。在过去的三十年中,人们对癫痫机制的理解有了很大的进展,特别是在其细胞和分子基础方面。然而,尽管有~30 种具有不同分子靶点的抗癫痫药物(AED)可用,但癫痫的药物治疗仍然存在许多挑战(例如耐药性、副作用)。由于分子机制在神经元回路水平上是整合的,我们建议将癫痫治疗和研究策略从“分子”水平转移到“回路”水平。最近的技术进步促进了每个水平的回路机制发现,并为许多新的治疗策略和 AED 开发提供了机会,以实现精确的回路治疗。

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