阿尔茨海默病的干预与α分泌酶ADAM10  

α secretase ADAM10 for therapy of Alzheimer＇s disease

作　　者：周婷[1] 于艳[1] 孙邈[1] 张希朦[1] 尹晨[1] 崔德华[1] 

机构地区：[1]教育部和卫生部神经科学重点实验室北京大学神经科学研究所,100191

出　　处：《神经疾病与精神卫生》2010年第6期541-545,共5页Journal of Neuroscience and Mental Health

基　　金：国家自然科学基金资助项目（30973145）;科技部973项目（2006CB500705）,博士点基金项目20090001110058, 北大医学部基础学院创新人才项目资助

摘　　要：阿尔茨海默病（Alzheimer＇s Disease, AD）是老年人最常见的神经变性疾病.整合素和金属蛋白酶10（ADAM10）是一种α分泌酶,也是淀粉样前体蛋白（APP）的代谢中的一种关键蛋白酶,在AD中具有重要作用.在过表达ADAM10的动物模型中发现这种金属蛋白酶可以促进学习记忆和突触生成.因此,ADAM10在神经退行性病（如AD）中是一个有价值的靶点.ADAM10有很多底物,其中以APP最为显著.因此在治疗性提高ADAM10α分泌酶活性时任何副作用都要纳入考虑的范畴.这篇综述总结了目前有关ADAM10的结构和功能的信息,并进一步探讨提高α分泌酶的表达和/或活性作为治疗靶点的可能性.Alzheimer＇s disease （AD） is the most prevalent neurodegenerative disorder, a neuro- pathological hallmark of the disease are the amyloid plaques, which are extracellular protein deposits found in the brain of AD patients. Proteases similar to a--secretase are essential for diverse physiological processes,such as embryonic development,cell adhesion and neuronal guidance. Previously, several pro- teases were suggested as candidate α-secretases for amyloid precursor protein （APP）, in particular members of the ADAM family（a disintegrin and metalloprotease）. A disintegrin and metalloproteinase 10 （ADAM10）is an α-secretase, also a key protease in the processing of the amyloid precursor protein. It plays an important role in Alzheimer＇s disease. Overexpression of ADAM10 in animal models revealed a beneficial effect of ADAM10 on learning, memory,and synaptogenesis. Therefore, ADAM10 appears to be a worthwhile target in the treatment of neurodegenerative disease, especially Alzheimer＇s disease. Since ADAM10 has many substrates, among which amyloid precursor protein is the most prominent, in the therapeutic enhancement of ADAM10 a--secretase activity, any side effect should be concerned. This review summarizes information about the structure and function of ADAM10, and further discusses the possibility of enhancing the expression and/or activity of the α-secretase as a therapeutic target.

关 键 词：α分泌酶 淀粉样前体蛋白 阿尔茨海默病 

分 类 号：R749.1[医药卫生—神经病学与精神病学]