title: Retromers in Alzheimer's disease.
abstract: Amyloid-β peptide (Aβ), the key pathogenic agent in Alzheimer's disease (AD), is released after sequential proteolytic cleavage of the transmembrane amyloid precursor protein (APP). β-Site APP-cleaving enzyme 1 (BACE1) cleaves APP in early endosomes, and the cause of increased BACE cleavage of APP in AD is not fully resolved yet. It has been proposed that perturbed intracellular trafficking of APP, which leads to prolonged residence time in early endosomes, influences Aβ production and hence the risk for AD. Retromers are a family of proteins that mediate the retrieval of transmembrane proteins from the endosomes to the trans-Golgi network. Misregulation of retromers or retromer-associated proteins influences endosomal localization of APP/BACE1. Here we review the role of retromers in the amyloidogenic processing of APP and their pathogenic role in AD.
authors.affiliation: Systems and Cell Biology of Neurodegeneration, Division of Psychiatry Research, University of Zurich, Zurich, Switzerland.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Siegenthaler
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rajendran
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D021381:Protein Transport; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D046912:Multiprotein Complexes; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human