Bruno VincentFrédéric CheclerUniversite Nice Sophia AntipolisMahidol University2018-06-112018-06-112012-02-01Current Alzheimer Research. Vol.9, No.2 (2012), 140-15618755828156720502-s2.0-84857704802https://repository.li.mahidol.ac.th/handle/20.500.14594/15005Proteases 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. © 2012 Bentham Science Publishers.Mahidol UniversityMedicineNeuroscienceReviewSCOPUS10.2174/156720512799361646