- Top of page
- APP α-secretase cleavage
- The ADAMs
- α-Secretase and ADAM17
- α-Secretase and ADAM10
- α-Secretase and ADAM9
- Comparative contribution to APP α-secretase cleavage by ADAM17, 10, and 9
- Other α-secretase candidates
- Mechanisms of regulation of APP α-secretase cleavage
- sAPPα as a neurotrophic and neuroprotective factor
- Conflict of interest
J. Neurochem. (2012) 120 (Suppl. 1), 34–45.
‘Secretase’ is a generic term coined more than 20 years ago to refer to a group of proteases responsible for the cleavage of a vast number of membrane proteins. These endoproteolytic events result in the extracellular or intracellular release of soluble metabolites associated with a broad range of intrinsic physiological functions. α-Secretase refers to the activity targeting the amyloid precursor protein (APP) and generating sAPPα, a soluble extracellular fragment potentially associated with neurotrophic and neuroprotective functions. Several proteases from the a disintegrin and metalloproteinase (ADAM) family, including ADAM10 and ADAM17, have been directly or indirectly associated with the constitutive and regulated α-secretase activities. Recent evidence in primary neuronal cultures indicates that ADAM10 may represent the genuine constitutive α-secretase. Mainly because α-secretase cleaves APP within the sequence of Aβ, the core component of the cerebral amyloid plaques in Alzheimer’s disease, α-secretase activation is considered to be of therapeutic value. In this article, we will provide a historical perspective on the characterization of α-secretase and review the recent literature on the identification and biology of the current α-secretase candidates.