Current Alzheimer Research

Prof. Debomoy K. Lahiri  
Department of Psychiatry, Indiana University School of Medicine
Neuroscience Research Center
Indianapolis, IN 46202


α-Secretase in Alzheimers Disease and Beyond: Mechanistic, Regulation and Function in the Shedding of Membrane Proteins

Author(s): Bruno Vincent and Frederic Checler

Affiliation: Institute of Molecular Biosciences,Center for Neuroscience, Mahidol University, Salaya campus, 999 Phuttamonthon 4 Road, Nakhon Pathom 73170, Thailand.


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.

Keywords: Disintegrin, metalloprotease, metabolism, Alzheimer regulation, transmembrane proteins, proprotein convertase cleavage, crambin-like domains, GPI-anchored substrates

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Article Details

Page: [140 - 156]
Pages: 17
DOI: 10.2174/156720512799361646