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Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family

Amyloid-β peptide (Aβ) accumulation in the brain is an early, toxic event in the pathogenesis of Alzheimer's disease (AD). Aβ is produced by proteolytic processing of a transmembrane protein, β-amyloid precursor protein (APP), by β- and γ-secretases. Mounting evidence has demonstrated that alte...

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Detalles Bibliográficos
Autores principales: Cam, Judy A, Bu, Guojun
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1563464/
https://www.ncbi.nlm.nih.gov/pubmed/16930455
http://dx.doi.org/10.1186/1750-1326-1-8
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author Cam, Judy A
Bu, Guojun
author_facet Cam, Judy A
Bu, Guojun
author_sort Cam, Judy A
collection PubMed
description Amyloid-β peptide (Aβ) accumulation in the brain is an early, toxic event in the pathogenesis of Alzheimer's disease (AD). Aβ is produced by proteolytic processing of a transmembrane protein, β-amyloid precursor protein (APP), by β- and γ-secretases. Mounting evidence has demonstrated that alterations in APP cellular trafficking and localization directly impact its processing to Aβ. Recent studies have shown that members of the low-density lipoprotein receptor family, including LRP, LRP1B, SorLA/LR11, and apolipoprotein E (apoE) receptor 2, interact with APP and regulate its endocytic trafficking. Another common feature of these receptors is their ability to bind apoE, which exists in three isoforms in humans and the presence of the ε4 allele represents a genetic risk factor for AD. In this review, we summarize the current understanding of the function of these apoE receptors with a focus on their role in APP trafficking and processing. Knowledge of the interactions between these distinct low-density lipoprotein receptor family members and APP may ultimately influence future therapies for AD.
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spelling pubmed-15634642006-09-09 Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family Cam, Judy A Bu, Guojun Mol Neurodegener Review Amyloid-β peptide (Aβ) accumulation in the brain is an early, toxic event in the pathogenesis of Alzheimer's disease (AD). Aβ is produced by proteolytic processing of a transmembrane protein, β-amyloid precursor protein (APP), by β- and γ-secretases. Mounting evidence has demonstrated that alterations in APP cellular trafficking and localization directly impact its processing to Aβ. Recent studies have shown that members of the low-density lipoprotein receptor family, including LRP, LRP1B, SorLA/LR11, and apolipoprotein E (apoE) receptor 2, interact with APP and regulate its endocytic trafficking. Another common feature of these receptors is their ability to bind apoE, which exists in three isoforms in humans and the presence of the ε4 allele represents a genetic risk factor for AD. In this review, we summarize the current understanding of the function of these apoE receptors with a focus on their role in APP trafficking and processing. Knowledge of the interactions between these distinct low-density lipoprotein receptor family members and APP may ultimately influence future therapies for AD. BioMed Central 2006-08-18 /pmc/articles/PMC1563464/ /pubmed/16930455 http://dx.doi.org/10.1186/1750-1326-1-8 Text en Copyright © 2006 Cam and Bu; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Cam, Judy A
Bu, Guojun
Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family
title Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family
title_full Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family
title_fullStr Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family
title_full_unstemmed Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family
title_short Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family
title_sort modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1563464/
https://www.ncbi.nlm.nih.gov/pubmed/16930455
http://dx.doi.org/10.1186/1750-1326-1-8
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