TY - JOUR
T1 - Lipoprotein receptors and cholesterol in APP trafficking and proteolytic processing, implications for Alzheimer's disease
AU - Marzolo, Maria Paz
AU - Bu, Guojun
PY - 2009/4
Y1 - 2009/4
N2 - Amyloid-β (Aβ) peptide accumulation in the brain is central to the pathogenesis of Alzheimer's disease (AD). Aβ is produced through 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. Members of the low-density lipoprotein receptor family, including LRP, LRP1B, SorLA/LR11, and apoER2, interact with APP and regulate its endocytic trafficking. Additionally, APP trafficking and processing are greatly affected by cellular cholesterol content. In this review, we summarize the current understanding of the roles of lipoprotein receptors and cholesterol in APP trafficking and processing and their implication for AD pathogenesis and therapy.
AB - Amyloid-β (Aβ) peptide accumulation in the brain is central to the pathogenesis of Alzheimer's disease (AD). Aβ is produced through 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. Members of the low-density lipoprotein receptor family, including LRP, LRP1B, SorLA/LR11, and apoER2, interact with APP and regulate its endocytic trafficking. Additionally, APP trafficking and processing are greatly affected by cellular cholesterol content. In this review, we summarize the current understanding of the roles of lipoprotein receptors and cholesterol in APP trafficking and processing and their implication for AD pathogenesis and therapy.
KW - Alzheimer's disease
KW - Amyloid precursor protein
KW - Amyloid-β peptide
KW - Cholesterol
KW - Lipoprotein receptors
UR - http://www.scopus.com/inward/record.url?scp=63949084694&partnerID=8YFLogxK
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U2 - 10.1016/j.semcdb.2008.10.005
DO - 10.1016/j.semcdb.2008.10.005
M3 - Review article
C2 - 19041409
AN - SCOPUS:63949084694
SN - 1084-9521
VL - 20
SP - 191
EP - 200
JO - Seminars in Cell and Developmental Biology
JF - Seminars in Cell and Developmental Biology
IS - 2
ER -