α-Secretase in Alzheimers Disease and Beyond: Mechanistic, Regulation and Function in the Shedding of Membrane Proteins
Bruno Vincent and Frederic Checler
Pages 140-156 (17)
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 Alzheimers 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 Alzheimers disease.
Disintegrin, metalloprotease, metabolism, Alzheimer regulation, transmembrane proteins, proprotein convertase cleavage, crambin-like domains, GPI-anchored substrates
Institute of Molecular Biosciences,Center for Neuroscience, Mahidol University, Salaya campus, 999 Phuttamonthon 4 Road, Nakhon Pathom 73170, Thailand.