Colivelin对PDAPP转基因AD小鼠抗Aβ毒性的研究

项目名称： Colivelin对PDAPP转基因AD小鼠抗Aβ毒性的研究

项目编号： No.81200247

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 尹榕

作者单位： 中国人民解放军兰州军区兰州总医院

项目金额： 22万元

中文摘要： 阿尔茨海默病（AD）是临床最为常见的老年痴呆类型。阐明AD发病机制，寻找特异性的抗AD防治措施是目前生物医学研究的热点和重点。β-淀粉样蛋白（Aβ）是AD形成和发展的关键因素。目前尚无特效治疗措施。Humanin（HN）是近年来新发现的内源性神经保护因子。体内、外的实验证实HN和它的衍生物对因Aβ引起的神经细胞毒性反应具有保护作用。Colivelin(CLN)是在活性依赖的神经营养因子（ADNF）C末端融合了AGA-HNG，同时通过2种途径发挥神经保护作用。本项研究将观察①经AGA-HNG与ADNF融合后合成的CLN对抗Aβ毒性的神经保护作用是否具有协同作用；②与加兰他敏治疗组比较，CLN是一种有效的抗Aβ毒性的神经保护肽段。分析CLN对于抗Aβ毒性神经保护作用的前景，将为开发防治AD新药物及其临床应用提供更为广阔的理论思路和客观的实验依据。

中文关键词： 阿尔茨海默病；Colivelin；记忆力减退；p38信号通路；

英文摘要： Alzheimer's disease(AD) is the most common senile dementia in clinic.It is a hot issue and trending topics now to clairfy the pathogenesis mechanism of AD and to search for specific preventive measures of AD on the biomedical sciences. β-amyloid protein(Aβ) is the key factor of AD formation and its development. At present spcific prevention measures haven't been got yet. Humanin(HN) is recently newfound endogenesis neuroprotective factor. The experiments in vivo and in vitro have proved that HN and its derivatives have protective effects on the nerve cell toxicity reaction caused by Aβ. Colivelin(CLN) is activity dependent neurotrophic factor(ADNF) C-terminal fused with AGA-HNG,and at the same time plays a neuroprotective role in two ways. This study will observe whether CLN synthesized by ADNF fused with AGA-HNG has the synergistic action against Aβtoxic neuroprotective effect or not;and will prove that CLN is a effective anti-Aβ toxic neuroprotective peptide,comparing with the galanthamine treatment group. Prospect analisis for anti-Aβ toxic neuroprotective effect of CLN will provide wider theoretical and objective experimental bases for developing new medicines used for protecting and treating AD, and for their clinical application.

英文关键词： Alzheimers’s disease；Colivelin；Memory dysfunction；p38 signaling pathway；