NMDA受体基因突变在儿童癫痫中的致病机制

癫痫是常见的儿科神经系统遗传性疾病。NMDA受体是神经系统重要的神经传递受体，由多种基因编码的亚基组成。这些基因的突变会导致NMDA受体活性的改变，从而导致神经元兴奋性和脑功能的改变。目前已知NMDA受体的基因突变是导致癫痫的一个重要遗传因素，但是对于其具体的致病机制还不清楚。阐明不同NMDA受体基因突变的致病机制，将有利于将不同突变进行分类，找到对应性药物，从而指导临床用药。本研究将针对临床发现的导致癫痫的NMDA受体基因的突变体，在细胞水平，组织水平和动物水平对突变的致病机制进行研究，并通过基因突变的功能影响分类，并用FDA批准的NMDA受体相关的药物进行处理，筛选出对各类突变有效的药物，并在临床上进行初步尝试。本项目有利于探索出一套从基础研究到临床的精准治疗方法。

Epilepsy is a common pediatric neurological diseases. NMDA receptor (NMDAR) is an important neurotransmitter receptor in brain. The mutations in genes which encode NMDAR have been found in epilepsy, indicating NMDAR take part in this disease. In this study, we will study NMDAR mutations, which we found from epilepsy patients. By the analysis of the bioinformatics, molecular biology, cell biology, electrophysiology as well as transgenic animal models, we will validate the effect of these mutations on NMDAR function and neuron excitability. Then, we also will test some FDA-approved NMDAR channel modulator on the mutant . Thus, we hope to clarify the mechanism of NMDAR mutations in epilepsy and try to find some FDA-approved NMDAR channel modulator could be clinically effective drug. The research on the pathogenesis of epilepsy will be helpful for the personalized treatment and precision medicine.