Institute of Molecular Biosciences, Center for Neuroscience, Mahidol University, Salaya campus, 999 Phuttamonthon 4 Road, Nakhon Pathom 73170, Thailand.
Curr Alzheimer Res. 2012 Feb;9(2):140-56. doi: 10.2174/156720512799361646.
Proteases regulate numerous physiological functions in all living organisms. Because of their contribution to βAPP processing, α-, β- and γ-secretases have focused particular attention of researchers in the field of Alzheimer's disease (AD) during the past 20 years. Whereas the β-secretase BACE1 and the heterotetrameric presenilin-dependent γ- secretase complex were identified between 1995 and 2002, α-secretase activity was attributed to previously described ADAM10 and ADAM17, two members of the type I integral membrane protein family called ADAMs (A Disintegrin And Metalloprotease). ADAM10 and/or ADAM17 target numerous substrates through various modes of action. This review focuses on the complex physiology of these α-secretases and will document their contribution to cancers, diabetes, rheumatoid arthritis, and prion diseases besides their well characterized role in Alzheimer's disease.
蛋白酶调节所有生物体的许多生理功能。由于它们对βAPP 加工的贡献，α-、β-和 γ- 分泌酶在过去 20 年中引起了阿尔茨海默病（AD）领域研究人员的特别关注。虽然 β- 分泌酶 BACE1 和多聚体依赖早老素的 γ- 分泌酶复合物在 1995 年至 2002 年间被鉴定出来，但 α- 分泌酶活性归因于先前描述的 ADAM10 和 ADAM17，这两种蛋白都是称为 ADAMs（解整合素和金属蛋白酶）的 I 型整合膜蛋白家族的成员。ADAM10 和/或 ADAM17 通过多种作用模式针对许多底物。这篇综述重点介绍了这些 α- 分泌酶的复杂生理学，并记录了它们除了在阿尔茨海默病中特征明显的作用外，对癌症、糖尿病、类风湿关节炎和朊病毒病的贡献。
