Yan Mengqi, Guo Xiongfeng, Xu Cenglin
Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, The Second Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Xinhua Hospital), Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Acta Epileptol. 2024 May 3;6(1):15. doi: 10.1186/s42494-024-00162-7.
Developmental and epileptic encephalopathies are severe neurological conditions in clinical practice, among which loss-of-function mutations in brain-enriched serine-threonine kinase cyclin dependent kinase like-5 (CDKL5) exists as one of the most common types. It is unknown, therefore, how precisely CDKL5 mutations lead to neuronal hyper-excitation. A recent study that looked at the connection between voltage-gated calcium channel Cav2.3 and CDKL5 in an experimental context was published in Nature Communications. This study has revealed that Cav2.3, a physiological phosphorylation target of CDKL5, would show delayed inactivation and increased cholinergic stimulation in CDKL5 knock out conditions. This would in turn cause neuronal hyperexcitability and related enhanced seizure susceptibility. This work, in our opinion, provided fresh insight into the epileptic encephalopathies linked to CDKL5 and highlighted Cav2.3 as a possible target for it.
发育性和癫痫性脑病是临床实践中严重的神经系统疾病，其中脑富集丝氨酸 - 苏氨酸激酶细胞周期蛋白依赖性激酶样5（CDKL5）功能丧失突变是最常见的类型之一。因此，尚不清楚CDKL5突变如何精确地导致神经元过度兴奋。最近一项在实验环境中研究电压门控钙通道Cav2.3与CDKL5之间联系的研究发表在《自然通讯》上。这项研究表明，Cav2.3作为CDKL5的生理磷酸化靶点，在CDKL5基因敲除条件下会表现出失活延迟和胆碱能刺激增加。这反过来会导致神经元过度兴奋和相关的癫痫易感性增强。我们认为，这项工作为与CDKL5相关的癫痫性脑病提供了新的见解，并突出了Cav2.3作为其可能的治疗靶点。
