Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland.
International College of Pharmaceutical Innovation, Soochow University, Suzhou 215123, China.
Int J Mol Sci. 2024 Jun 23;25(13):6894. doi: 10.3390/ijms25136894.
Epilepsy is one of the most common neurological diseases worldwide. Anti-seizure medications (ASMs) with anticonvulsants remain the mainstay of epilepsy treatment. Currently used ASMs are, however, ineffective to suppress seizures in about one third of all patients. Moreover, ASMs show no significant impact on the pathogenic mechanisms involved in epilepsy development or disease progression and may cause serious side-effects, highlighting the need for the identification of new drug targets for a more causal therapy. Compelling evidence has demonstrated a role for purinergic signalling, including the nucleotide adenosine 5'-triphosphate (ATP) during the generation of seizures and epilepsy. Consequently, drugs targeting specific ATP-gated purinergic receptors have been suggested as promising treatment options for epilepsy including the cationic P2X7 receptor (P27XR). P2X7R protein levels have been shown to be increased in the brain of experimental models of epilepsy and in the resected brain tissue of patients with epilepsy. Animal studies have provided evidence that P2X7R blocking can reduce the severity of acute seizures and the epileptic phenotype. The current review will provide a brief summary of recent key findings on P2X7R signalling during seizures and epilepsy focusing on the potential clinical use of treatments based on the P2X7R as an adjunctive therapeutic strategy for drug-refractory seizures and epilepsy.
癫痫是全球最常见的神经系统疾病之一。具有抗惊厥作用的抗癫痫药物（ASM）仍然是癫痫治疗的主要方法。然而，目前使用的 ASM 在大约三分之一的患者中无法有效抑制癫痫发作。此外，ASM 对癫痫发展或疾病进展中涉及的致病机制没有显著影响，并且可能会引起严重的副作用，这凸显了需要确定新的药物靶点，以进行更具因果关系的治疗。有强有力的证据表明，嘌呤能信号包括核苷酸三磷酸腺苷（ATP）在癫痫发作和癫痫的发生中发挥作用。因此，针对特定 ATP 门控嘌呤能受体的药物已被认为是癫痫的有前途的治疗选择，包括阳离子 P2X7 受体（P27XR）。已经表明，癫痫实验模型的大脑中和癫痫患者的切除脑组织中 P2X7R 蛋白水平增加。动物研究提供了证据表明，P2X7R 阻断可以减轻急性癫痫发作的严重程度和癫痫表型。本综述将简要总结最近关于 P2X7R 信号在癫痫发作和癫痫中的关键发现，重点介绍基于 P2X7R 的治疗作为治疗耐药性癫痫发作和癫痫的辅助治疗策略的潜在临床应用。
