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- W2023182330 abstract "The Aβ peptide that accumulates in Alzheimer's disease (AD) is derived from amyloid precursor protein (APP) following proteolysis by β- and γ-secretases. Substansive evidence indicates that alterations in APP trafficking within the secretory and endocytic pathways directly impact the interaction of APP with these secretases and subsequent Aβ production. Various members of the low-density lipoprotein receptor (LDLR) family have been reported to play a role in APP trafficking and processing and are important risk factors in AD. We recently characterized a distinct member of the LDLR family called LDLR-related protein 10 (LRP10) that shuttles between the trans-Golgi Network (TGN) and endosomes. Here we investigate whether LRP10 participate in APP intracellular trafficking and Aβ production. Studies were performed mainly in human neuroblastoma cells (SH-SY5Y) stably expressing LRP10 wild-type or trafficking mutant. Protein interactions were determined by immunoprecipitation and pull-down assays. The subcellular localizations were characterized by confocal microscopy. APP processing products were determined by WB and ELISA. LRP10 interacts directly with APP and colocalizes with APP at the TGN. Increased expression of LRP10 induces the accumulation of mature APP in the Golgi and reduces its processing into Aβ, while knockdown of LRP10 expression increases Aβ production. Mutations of key motifs responsible for the recycling of LRP10 to the TGN results in the aberrant redistribution of APP with LRP10 to early endosomes and a concomitant increase in APP β-cleavage into Aβ. Furthermore, expression of LRP10 is significantly reduced in the post-mortem brain tissues of AD patients, supporting a possible role for LRP10 in AD. This study identifies LRP10 as a novel APP sorting receptor that protects APP from amyloidogenic processing, suggesting that a decrease in LRP10 function may contribute to the pathogenesis of Alzheimer's disease." @default.
- W2023182330 created "2016-06-24" @default.
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- W2023182330 date "2012-07-01" @default.
- W2023182330 modified "2023-09-27" @default.
- W2023182330 title "O5-01-03: LDLR-related protein 10 (LRP10) alters amyloid precursor protein (APP) trafficking and processing: evidence for a role in Alzheimer's disease" @default.
- W2023182330 doi "https://doi.org/10.1016/j.jalz.2012.05.1971" @default.
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