講座主題：Modulating the Balance of Synaptic and Extrasynaptic NMDA Receptors as a strategy for Alzheimer's disease drug discovery
主講人：周文霞
工作單位：軍事醫(yī)學(xué)科學(xué)院
講座時間：2019年5月24日14:30
講座地點：藥學(xué)院一樓報告廳
主辦單位：煙臺大學(xué)藥學(xué)院
內(nèi)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.
主講人介紹：
周文霞，博士，研究員，博士生導(dǎo)師，軍事科學(xué)院軍事醫(yī)學(xué)研究院毒物藥物研究所中藥和神經(jīng)免疫藥理研究室主任。主要從事中藥藥理、神經(jīng)藥理、免疫藥理及網(wǎng)絡(luò)藥理學(xué)研究以及新藥研發(fā)。作為課題負(fù)責(zé)人曾先后承擔(dān)多項國家軍隊重點或重大課題，主要包括國家973項目課題、國家自然科學(xué)基金面上項目和重大研究計劃項目、國家重大新藥創(chuàng)制重大專項課題和國家科技支撐計劃課題等。獲北京市科學(xué)技術(shù)獎一等獎1項、軍隊及上海市科技進(jìn)步二等獎3項，發(fā)表學(xué)術(shù)論文180余篇（SCI收錄90余篇），主編（副主編）專著2部，參編3部，申請專利28項，授權(quán)15項 ，獲新藥臨床批件 2 項，曾被評為全國優(yōu)秀科技工作者。現(xiàn)任中國藥理學(xué)會副秘書長、常務(wù)理事、網(wǎng)絡(luò)藥理專業(yè)委員會主任委員等職。
