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Retromers in Alzheimer's disease


Siegenthaler, Barbara; Rajendran, Lawrence (2012). Retromers in Alzheimer's disease. Neurodegenerative Diseases, 10(1-4):116-121.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:04 Jul 2012 11:00
Last Modified:28 Aug 2016 07:19
Publisher:Karger
ISSN:1660-2854
Publisher DOI:https://doi.org/10.1159/000335910
PubMed ID:22398391

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