Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family
Open Access
- 1 January 2006
- journal article
- Published by Springer Science and Business Media LLC in Molecular Neurodegeneration
- Vol. 1 (1), 8
- https://doi.org/10.1186/1750-1326-1-8
Abstract
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.Keywords
This publication has 98 references indexed in Scilit:
- Modulation of Synaptic Plasticity and Memory by Reelin Involves Differential Splicing of the Lipoprotein Receptor Apoer2Neuron, 2005
- Loss of Apolipoprotein E Receptor LR11 in Alzheimer DiseaseArchives of Neurology, 2004
- The Low Density Lipoprotein Receptor-related Protein 1B Retains β-Amyloid Precursor Protein at the Cell Surface and Reduces Amyloid-β Peptide ProductionPublished by Elsevier BV ,2004
- The cytoplasmic domain of the LDL receptor-related protein regulates multiple steps in APP processingThe EMBO Journal, 2002
- Reelin and ApoE Receptors Cooperate to Enhance Hippocampal Synaptic Plasticity and LearningJournal of Biological Chemistry, 2002
- Interactions of the Low Density Lipoprotein Receptor Gene Family with Cytosolic Adaptor and Scaffold Proteins Suggest Diverse Biological Functions in Cellular Communication and Signal TransductionJournal of Biological Chemistry, 2000
- Modulation of β-Amyloid Precursor Protein Processing by the Low Density Lipoprotein Receptor-related Protein (LRP)Journal of Biological Chemistry, 2000
- Cell Surface Presenilin-1 Participates in the γ-Secretase-like Proteolysis of NotchJournal of Biological Chemistry, 1999
- Interaction of Cytosolic Adaptor Proteins with Neuronal Apolipoprotein E Receptors and the Amyloid Precursor ProteinJournal of Biological Chemistry, 1998
- Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's diseaseNature, 1991