The Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
Int J Mol Sci. 2023 Feb 2;24(3):2928. doi: 10.3390/ijms24032928.
The pharmacological treatment of epilepsy is purely symptomatic. Despite many decades of intensive research, causal treatment of this common neurologic disorder is still unavailable. Nevertheless, it is expected that advances in modern neuroscience and molecular biology tools, as well as improved animal models may accelerate designing antiepileptogenic and epilepsy-modifying drugs. Epileptogenesis triggers a vast array of genomic, epigenomic and transcriptomic changes, which ultimately lead to morphological and functional transformation of specific neuronal circuits resulting in the occurrence of spontaneous convulsive or nonconvulsive seizures. Recent decades unraveled molecular processes and biochemical signaling pathways involved in the proepileptic transformation of brain circuits including oxidative stress, apoptosis, neuroinflammatory and neurotrophic factors. The "omics" data derived from both human and animal epileptic tissues, as well as electrophysiological, imaging and neurochemical analysis identified a plethora of possible molecular targets for drugs, which could interfere with various stages of epileptogenetic cascade, including inflammatory processes and neuroplastic changes. In this narrative review, we briefly present contemporary views on the neurobiological background of epileptogenesis and discuss the advantages and disadvantages of some more promising molecular targets for antiepileptogenic pharmacotherapy.
癫痫的药物治疗纯属对症治疗。尽管经过了几十年的深入研究,但这种常见的神经系统疾病仍缺乏病因治疗方法。然而,预计现代神经科学和分子生物学工具的进步以及改进的动物模型可能会加速抗癫痫发生和改变癫痫的药物的设计。癫痫发生引发了广泛的基因组、表观基因组和转录组变化,最终导致特定神经元回路的形态和功能发生转变,从而导致自发性惊厥或非惊厥性发作的发生。近几十年来,人们揭示了涉及脑回路致痫性转化的分子过程和生化信号通路,包括氧化应激、细胞凋亡、神经炎症和神经营养因子。从人类和动物癫痫组织以及电生理学、影像学和神经化学分析中获得的“组学”数据确定了大量可能的药物分子靶点,这些靶点可以干扰癫痫发生级联的各个阶段,包括炎症过程和神经可塑性变化。在本综述中,我们简要介绍了癫痫发生的神经生物学背景的现代观点,并讨论了一些更有前途的抗癫痫发生药物治疗的分子靶点的优缺点。