Lipoprotein receptors and cholesterol in APP trafficking and proteolytic processing, implications for Alzheimer's disease.
Amyloid-beta (Abeta) peptide accumulation in the brain is central to the pathogenesis of Alzheimer's disease (AD). Abeta is produced through proteolytic processing of a transmembrane protein, beta-amyloid precursor protein (APP), by beta- and gamma-secretases. Mounting evidence has demonstrated that alterations in APP cellular trafficking and localization directly impact its processing to Abeta. 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.
Marzolo
Maria-Paz
MP
FONDAP Center for Cell Regulation and Pathology (CRCP), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile and MIFAB, Santiago, Chile.
Bu
Guojun
G
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011973:Receptors, LDL / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011973:Receptors, LDL; D002784:Cholesterol