TY - JOUR
T1 - Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family
AU - Cam, Judy A.
AU - Bu, Guojun
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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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U2 - 10.1186/1750-1326-1-8
DO - 10.1186/1750-1326-1-8
M3 - Article
AN - SCOPUS:34248202513
SN - 1750-1326
VL - 1
JO - Molecular neurodegeneration
JF - Molecular neurodegeneration
IS - 1
M1 - 8
ER -