Keynote Lecture IV
The study of anti-Aβ31-35 single chain antibody in alzheimer's disease APP/PS1 transgenic mice
Qi Jinshun
Shanxi Medical University
Professor Jinshun Qi is Professor of Physiology at Shanxi Medical University and a Principal Investigator of Key Laboratory of Cellular Physiology, Ministry of Education. He graduated from Changzhi Medical College in 1980, and received his Master’s Degree from Tianjin Medical College in 1990. He got his PhD from Shanxi Medical University under the supervision of Professor Jiantian Qiao in 2000. He finished postdoctoral research in Penn State University during 2003-2006 and visited Hong Kong University Medical College in 2008 as a Dr Cheng Yu Tung fellow. He became Professor of Physiology and established his Laboratory of Neurophysiology in 2000. He was elected an executive council member of the Chinese Association for Physiological Sciences in 2010. He is interested in understanding the cellular and molecular pathogenesis of Alzheimer’s Disease (AD) using a combination of behavioral, molecular and electrophysiological techniques, with a specific focus on the active center of amyloid beta peptide (Aβ), an important biomarker in the AD brain. His group has helped to pioneer several new approaches including in vivo hippocampal long term potentiation (LTP) recording and brain slice non-invasive micro-test (NMT). With these techniques, they indicated the shortest active center of Aβ and investigated the neuroprotection of some peptide and a novel single chain anti-Aβ 31-35 antibody scFv17 in transgenic AD animals.
祁金順，男，1955年2月生，山西醫科大學生理學系教授，博士生導師，細胞生理學山西省重點實驗室主任。兼任中國生理學會常務理事、中國神經科學學會理事、《生理學報》及《生理科學進展》編委。1981年長治醫學院畢業，1990年獲天津醫科大學碩士學位，2000年獲山西醫科大學博士學位，2003年—2006年在美國賓夕法尼亞州立大學做博士後，2008年10月—12月在香港大學醫學院做訪問學者（鄭裕彤博士獎助金資助）。目前主要從事阿爾茨海默病的神經生物學基礎研究。主持國家和省部級科研項目10多項，發表研究論文100多篇。獲山西省自然科學一等獎1項、二等獎2項、山西省教學成果一等獎1項、國家發明專利和實用新型專利各1項，均為負責人。培養研究生40多名，其中博士15名。
Abstract
Although with some side effects, the immunotherapy for AD is still promising in improving cognition and memory by clearing amyloid β protein (Aβ) in the AD brain. Our previous researches have shown that the sequence 31-35 in the Aβ molecule could be the shortest active center with neurotoxicity, and a polyclonal antibody against Aβ31-35 reduced neuronal apoptosis and cognitive impairments induced by Aβ direct injection. Recently, we designed a novel single-chain variable fragment (scFv) monoclonal anti-Aβ31-35 antibody (scFv17) which specifically recognizes the extracellular Aβ, not affecting membrane-bound amyloid precursor protein (APP). By using APP/PS1 transgenic mice, we investigated the effects of the scFv17 on the spatial learning and memory, the hippocampal synaptic plasticity and the AD pathological charecteristics in the brain. Our results showed that the anti-Aβ31-35 scFv17, by reducing Aβ pathology and increasing anti-inflammation, improved the synaptic plasticity and spatial memory of the APP/PS1 transgenic mice, suggesting the scFv17 may be a novel alternative to current immunotherapy of AD.
阿爾茨海默病（AD）的免疫學治療儘管存在一些副作用，但仍然是目前清除AD患者腦內病理性澱粉樣斑塊A和改善認知功能最有希望的療法。我們先前的研究顯示，A分子中的序列是其發揮毒性作用的活性中心，抗Aβ31-35多克隆抗體能夠減少Aβ所致的神經元凋亡和認知傷害。最近，我們設計了一種新的單克隆抗Aβ31-35單鏈抗體scFv17，其能夠特異性識別細胞外的Aβ，而不影響跨膜蛋白APP。通過使用APP/PS1轉基因AD小鼠，我們研究了scFv17對其學習記憶行為、海馬突觸可塑性和腦內AD病理特徵的影響。結果顯示：抗Aβ31-35抗體 scFv17通過減輕小鼠腦內的病理性澱粉樣斑塊和增加抗炎因數，改善了AD小鼠的突觸可塑性和空間記憶功能，提示這種新型單鏈抗體scFv17有可能成為AD免疫學治療的一種新手段。