α分泌酶在阿尔茨海默病治疗中的作用

Therapeutic Potential of α-Secretase in Alzheimer's Disease

阿尔茨海默病(Alzheimer!sdisease,AD)是老年人常见的一种神经系统变性疾病,其特征性病理变化是患者脑内的神经炎性斑,神经炎性斑的主要成分是细胞外β淀粉样蛋白(βamyloid,Aβ)的沉积.Aβ由其前体物质——淀粉样前体蛋白(amyloidprecursorprotein,APP)经β分泌酶和γ分泌酶系列水解而来.APP也可在α分泌酶和γ分泌酶的序列作用下水解,既避免了完整Aβ分子的产生,又产生了对细胞有益的胞外片段(sAPPα),因此这条代谢途径已成为研究AD治疗的靶点.较多的实验结果显示,一类解聚素和金属蛋白酶(adisintegrinandmetalloproteinase,ADAM)分子具有α分泌酶的功能,α分泌酶有可能成为AD治疗的潜在药物靶点.

Alzheimeds disease （AD） is one of the commonest neurodegenerative diseases affected mainly the elderly. AD is characterized by the formation of neuritic plaque in brain, which is composed mainly of extracellular β amyloid deposion, the Aβ. Aβ is deprived from serial hydrolysis of amyloid precursor protein （APP） by two secretases, the β and γ-secretase respectively. Alternatively, APP can also be sequential processed by α-secretase and β-secretase, which not only preclude the formation of Aβ, but also generate a large ectodomain （sAPPα） who has several neuroprotective properties. Thus the secondary processing pathway has become the focus of AD research. Many results have indicated that members of the adamalysin family of proteins, mainly the ADAM 10, ADAM 17 and ADAM 9, fulfill some of the criteria required of α-secretase. Here the biological characteristics of α-secretase, its activity regulation and its potential function as targets for the treatment of AD were summerized.