title: A Greek Tragedy: The Growing Complexity of Alzheimer Amyloid Precursor Protein Proteolysis.
abstract: Proteolysis of the amyloid precursor protein (APP) liberates various fragments including the proposed initiator of Alzheimer disease-associated dysfunctions, amyloid-β. However, recent evidence suggests that the accepted view of APP proteolysis by the canonical α-, β-, and γ-secretases is simplistic, with the discovery of a number of novel APP secretases (including δ- and η-secretases, alternative β-secretases) and additional metabolites, some of which may also cause synaptic dysfunction. Furthermore, various proteins have been identified that interact with APP and modulate its cleavage by the secretases. Here, we give an overview of the increasingly complex picture of APP proteolysis.
authors.affiliation: From the Departments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, Illinois 60637 and rjandrew@uchicago.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Andrew
authors.affiliation: the Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Katherine A B
authors.initials: KA
authors.lastname: Kellett
authors.affiliation: From the Departments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, Illinois 60637 and.
authors.forename: Gopal
authors.initials: G
authors.lastname: Thinakaran
authors.affiliation: the Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom nigel.hooper@manchester.ac.uk.
authors.forename: Nigel M
authors.identifier: 0000-0002-5811-3484
authors.initials: NM
authors.lastname: Hooper
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D006801:Humans; D059748:Proteolysis
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases
keywords: ADAM; ADAM10; Alzheimer disease; amyloid; amyloid precursor protein (APP); amyloid-beta (AB); beta-secretase 1 (BACE1); cathepsin B (CTSB); presenilin; protease; proteolysis; secretase