title: Identification and biology of α-secretase.
abstract: '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.
authors: Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
authors: Valérie
authors: V
authors: Vingtdeux
authors: Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
authors: Philippe
authors: P
authors: Marambaud
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000302:isolation & purification* / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D006801:Humans; D058225:Plaque, Amyloid / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D020033:Protein Isoforms; D053829:Amyloid Precursor Protein Secretases