alpha-Secretase in Alzheimer%26apos;s Disease and Beyond: Mechanistic, Regulation and Function in the Shedding of Membrane Proteins

作者：Vincent Bruno^*; Checler Frederic

来源：Current Alzheimer Research, 2012, 9(2): 140-156.

DOI：10.2174/156720512799361646

• Disintegrin
• metalloprotease
• metabolism
• Alzheimer
• regulation
• transmembrane proteins

Proteases regulate numerous physiological functions in all living organisms. Because of their contribution to beta APP processing, alpha-, beta- and gamma-secretases have focused particular attention of researchers in the field of Alzheimer%26apos;s disease (AD) during the past 20 years. Whereas the beta -secretase BACE1 and the heterotetrameric presenilin-dependent gamma-secretase complex were identified between 1995 and 2002, alpha-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 alpha-secretases and will document their contribution to cancers, diabetes, rheumatoid arthritis, and prion diseases besides their well characterized role in Alzheimer%26apos;s disease.

• 出版日期2012-2