Dixit Aparna Banerjee, Banerjee Jyotirmoy, Tripathi Manjari, Sarkar Chitra, Chandra P Sarat
Center for Excellence in Epilepsy, A Joint National Brain Research Centre (NBRC)- All India Institute of Medical Sciences (AIIMS) Collaboration, NBRC, Gurugram, India.
Department of Neurology, AIIMS, New Delhi, India.
Indian J Med Res. 2017 Feb;145(2):179-188. doi: 10.4103/ijmr.IJMR_1249_14.
There is an urgent need to understand the molecular mechanisms underlying epilepsy to find novel prognostic/diagnostic biomarkers to prevent epilepsy patients at risk. Cyclin-dependent kinase 5 (CDK5) is involved in multiple neuronal functions and plays a crucial role in maintaining homeostatic synaptic plasticity by regulating intracellular signalling cascades at synapses. CDK5 deregulation is shown to be associated with various neurodegenerative diseases such as Alzheimer's disease. The association between chronic loss of CDK5 and seizures has been reported in animal models of epilepsy. Genetic expression of CDK5 at transcriptome level has been shown to be abnormal in intractable epilepsy. In this review various possible mechanisms by which deregulated CDK5 may alter synaptic transmission and possibly lead to epileptogenesis have been discussed. Further, CDK5 has been proposed as a potential biomarker as well as a pharmacological target for developing treatments for epilepsy.
迫切需要了解癫痫背后的分子机制，以寻找新的预后/诊断生物标志物，从而预防有风险的癫痫患者。细胞周期蛋白依赖性激酶5（CDK5）参与多种神经元功能，并通过调节突触处的细胞内信号级联反应，在维持稳态突触可塑性方面发挥关键作用。CDK5失调与多种神经退行性疾病如阿尔茨海默病有关。在癫痫动物模型中，已报道CDK5长期缺失与癫痫发作之间存在关联。在难治性癫痫中，CDK5在转录组水平的基因表达已显示异常。在本综述中，已讨论了CDK5失调可能改变突触传递并可能导致癫痫发生的各种可能机制。此外，CDK5已被提议作为一种潜在的生物标志物以及开发癫痫治疗方法的药理学靶点。
