TY - JOUR
T1 - LRP and Alzheimer's disease
AU - Zerbinatti, Celina V.
AU - Bu, Guojun
PY - 2005
Y1 - 2005
N2 - The low-density lipoprotein receptor (LDLR)-related protein, LRP, is a unique member of the LDLR family. Frequently referred to as a scavenger receptor, LRP is a large transmembrane endocytic receptor that can bind and internalize many functionally distinct ligands. Besides its role as a cargo-receptor, LRP has also been implicated in many signaling pathways. LRP knockout mice die at early embryonic age, which strongly suggests that LRP's functions are essential for normal development. Within the CNS, LRP is highly expressed in neuronal cell bodies and dendritic processes. In vitro, neurite outgrowth is stimulated by apolipoprotein E (apoE)-containing lipoprotein particles via binding to LRP. ApoE is the major cholesterol transporter in the brain and human carriers of one or two copies of the ε4 allele of apoE are at a higher risk of developing Alzheimer's disease (AD). LRP also binds the amyloid precursor protein (APP) and its proteolytic fragment, the amyloid-β peptide (Aβ), which are major players in the pathogenesis of AD. Finally, LRP has been linked to AD by genetic evidence. In this review we discuss the potential mechanisms by which LRP can affect APP and Aβ metabolism, and therefore contribute to the pathogenesis of AD.
AB - The low-density lipoprotein receptor (LDLR)-related protein, LRP, is a unique member of the LDLR family. Frequently referred to as a scavenger receptor, LRP is a large transmembrane endocytic receptor that can bind and internalize many functionally distinct ligands. Besides its role as a cargo-receptor, LRP has also been implicated in many signaling pathways. LRP knockout mice die at early embryonic age, which strongly suggests that LRP's functions are essential for normal development. Within the CNS, LRP is highly expressed in neuronal cell bodies and dendritic processes. In vitro, neurite outgrowth is stimulated by apolipoprotein E (apoE)-containing lipoprotein particles via binding to LRP. ApoE is the major cholesterol transporter in the brain and human carriers of one or two copies of the ε4 allele of apoE are at a higher risk of developing Alzheimer's disease (AD). LRP also binds the amyloid precursor protein (APP) and its proteolytic fragment, the amyloid-β peptide (Aβ), which are major players in the pathogenesis of AD. Finally, LRP has been linked to AD by genetic evidence. In this review we discuss the potential mechanisms by which LRP can affect APP and Aβ metabolism, and therefore contribute to the pathogenesis of AD.
KW - APP
KW - Alzheimer's disease
KW - Amyloid-β peptide
KW - ApoE
KW - Endocytosis
KW - LRP
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U2 - 10.1515/REVNEURO.2005.16.2.123
DO - 10.1515/REVNEURO.2005.16.2.123
M3 - Review article
C2 - 15959937
AN - SCOPUS:20444374712
SN - 0334-1763
VL - 16
SP - 123
EP - 135
JO - Reviews in the Neurosciences
JF - Reviews in the Neurosciences
IS - 2
ER -