讲座主题：Modulating the Balance of Synaptic and Extrasynaptic NMDA Receptors as a strategy for Alzheimer's disease drug discovery
主讲人：周文霞
工作单位：军事医学科学院
讲座时间：2019年5月24日14:30
讲座地点：药学院一楼报告厅
主办单位：99精品视频在线观看药学院
内容摘要：
The unbalance between synaptic (GluN2A, mediating the protective pathway) and extrasynaptic NMDA receptors (NMDARs) (GluN2B, mediating the excitotoxic pathway) has been found in Alzheimer’s disease (AD), indicating restoring the balance of GluN2A and GluN2B should be beneficial for AD therapy. In this study, the GluN2B-selective antagonist, ifenprodil, and the non-selective NMDAR agonist, NMDA, had little effects on amyloid-beta (Abeta)-induced long-term potentiation (LTP) deficits. Enhancing the activity of GluN2A had a protective effect against Abeta, and specific activation of GluN2A and inhibition of GluN2B showed a better protective effect. The combination of ifenprodil and D-cycloserine (a co-activator of NMDRs similar to D-serine) led to greater improvement in behavior tests than ifenprodil or D-cycloserine alone, meanwhile, the combination of ifenprodil and D-cycloserine reversed the signal pathway more significantly than ifenprodil or D-cycloserine alone. These results indicate that enhancing synaptic NMDARs and inhibiting extrasynaptic NMDARs concurrently showed protective effects against Abeta-induced neurotoxicity, suggesting that modulation of the balance between GluN2A and GluN2B might be a good strategy for drug discovery against AD.
主讲人介绍：
周文霞，博士，研究员，博士生导师，军事科学院军事医学研究院毒物药物研究所中药和神经免疫药理研究室主任。主要从事中药药理、神经药理、免疫药理及网络药理学研究以及新药研发。作为课题负责人曾先后承担多项国家军队重点或重大课题，主要包括国家973项目课题、国家自然科学基金面上项目和重大研究计划项目、国家重大新药创制重大专项课题和国家科技支撑计划课题等。获北京市科学技术奖一等奖1项、军队及上海市科技进步二等奖3项，发表学术论文180余篇（SCI收录90余篇），主编（副主编）专著2部，参编3部，申请专利28项，授权15项 ，获新药临床批件 2 项，曾被评为全国优秀科技工作者。现任中国药理学会副秘书长、常务理事、网络药理专业委员会主任委员等职。
