Department of Neurosurgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
Department of Neurusurgery & Key Laboratory, Shanghai Pudong New area People's Hospital, Shanghai, 201299, China.
Metab Brain Dis. 2022 Apr;37(4):881-887. doi: 10.1007/s11011-022-00909-6. Epub 2022 Feb 4.
Epilepsy is one of the most severe neurological disorders characterized by spontaneous recurrent seizures. Although more than two-thirds of patients can be cured with anti-epileptic drugs (AEDs), the rest one-third of epilepsy patients are resistant to AEDs. A series of studies have demonstrated Rho/Rho-associated kinase (ROCK) pathway might be involved in the pathogenesis of epilepsy in the recent twenty years. Several related pathway inhibitors of Rho/ROCK have been used in the treatment of epilepsy. We searched PubMed from Jan 1, 2000 to Dec 31, 2020, using the terms "epilepsy AND Rho AND ROCK" and "seizure AND Rho AND ROCK". We selected articles that characterized Rho/ROCK in animal models of epilepsy and patients. We then chose the most relevant research studies including in-vitro, in-vivo and clinical trials. The expression of Rho/ROCK could be a potential non-invasive biomarker to apply in treatment for patients with epilepsy. RhoA and ROCK show significant upregulation in the acute and chronic stage of epilepsy. ROCK inhibitors can reduce the epilepsy, epileptic seizure-related neuronal death and comorbidities. These findings demonstrate the novel development for diagnosis and treatment for patients with epilepsy. Rho/ROCK signaling pathway inhibitors may show more promising effects in epilepsy and related neurological diseases.
癫痫是最严重的神经障碍之一，其特征是自发性反复发作。尽管超过三分之二的患者可以通过抗癫痫药物（AEDs）治愈，但其余三分之一的癫痫患者对 AEDs 有抗药性。近二十年来，一系列研究表明 Rho/Rho 相关激酶（ROCK）通路可能与癫痫的发病机制有关。已经有几种 Rho/ROCK 相关通路抑制剂被用于治疗癫痫。我们从 2000 年 1 月 1 日至 2020 年 12 月 31 日在 PubMed 上搜索了使用术语“癫痫 AND Rho AND ROCK”和“发作 AND Rho AND ROCK”的文章。我们选择了描述癫痫动物模型和患者中 Rho/ROCK 的文章。然后，我们选择了最相关的研究，包括体外、体内和临床试验。Rho/ROCK 的表达可能是一种潜在的非侵入性生物标志物，可用于治疗癫痫患者。RhoA 和 ROCK 在癫痫的急性和慢性阶段均显著上调。ROCK 抑制剂可减少癫痫、癫痫发作相关神经元死亡和合并症。这些发现为癫痫患者的诊断和治疗提供了新的发展方向。Rho/ROCK 信号通路抑制剂可能在癫痫和相关神经疾病中显示出更有希望的效果。
