Shedding activity and physiological role of a newly-found ADAM family metalloprotease family

阿尔茨海默病的神经退行性变可能是由淀粉样β肽（Aβ）沉积在脑组织斑块中引起的。大脑中 Aβ 产生的机制一直是人们相当感兴趣的主题。多种因素调节淀粉样前体蛋白 (APP) 的加工，该蛋白由三种类型的膜结合蛋白酶（称为 α-、β- 和 γ-分泌酶）裂解。尽管我们才刚刚开始了解其功能，但非淀粉样蛋白α-分泌酶的发现已经为阿尔茨海默病药物开发中长期存在的问题提供了一些答案。在这里，我们总结了 APP α-分泌酶鉴定的最新进展。 α-分泌酶的药理学上调应该为阿尔茨海默氏病的合理药物设计提供依据。

The neurodegeneration in Alzheimer's disease may be caused by deposition of amyloid β peptide (Aβ) in plaques in brain tissue. Mechanisms of Aβ production in the brain have been the subject of considerable interest. Several factors regulate processing of amyloid precursor protein (APP), which is cleaved by three types of membrane-bound proteases designated α-, β-, and γ-secretases. Although we are only beginning to understand their function the discovery of nonamyloidogenic α-secretase has already provided some answers to longstanding questions of Alzheimer drug development. Here we summarize recent advances in the identification of APP α-secretases. Pharmacological up-regulation of α-secretases should provide rational drug design for Alzheimer's disease.