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(shí)間：2019年5月24日14:30
講座地點(diǎn)：藥學(xué)院一樓報(bào)告廳
主辦單位：煙臺(tái)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(xiàng)國(guó)家軍隊(duì)重點(diǎn)或重大課題，主要包括國(guó)家973項(xiàng)目課題、國(guó)家自然科學(xué)基金面上項(xiàng)目和重大研究計(jì)劃項(xiàng)目、國(guó)家重大新藥創(chuàng)制重大專項(xiàng)課題和國(guó)家科技支撐計(jì)劃課題等。獲北京市科學(xué)技術(shù)獎(jiǎng)一等獎(jiǎng)1項(xiàng)、軍隊(duì)及上海市科技進(jìn)步二等獎(jiǎng)3項(xiàng)，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(qǐng)專利28項(xiàng)，授權(quán)15項(xiàng) ，獲新藥臨床批件 2 項(xiàng)，曾被評(píng)為全國(guó)優(yōu)秀科技工作者?，F(xiàn)任中國(guó)藥理學(xué)會(huì)副秘書長(zhǎng)、常務(wù)理事、網(wǎng)絡(luò)藥理專業(yè)委員會(huì)主任委員等職。
