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LDLR-related protein 10 (LRP10) regulates amyloid precursor protein (APP) trafficking and processing: evidence for a role in Alzheimer’s disease

机译:LDLR相关蛋白10(LRP10)调节淀粉样前体蛋白(APP)的运输和加工:在阿尔茨海默氏病中起作用的证据

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摘要

BackgroundThe Aβ peptide that accumulates in Alzheimer’s disease (AD) is derived from amyloid precursor protein (APP) following proteolysis by β- and γ-secretases. Substantial 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), plasma membrane (PM), and endosomes. Here we investigated whether LRP10 participates in APP intracellular trafficking and Aβ production.
机译:背景阿尔茨海默氏病(AD)中积累的Aβ肽是由β和γ分泌酶进行蛋白水解后衍生自淀粉样前体蛋白(APP)的产物。大量证据表明,分泌途径和胞吞途径内APP转运的改变直接影响APP与这些分泌酶的相互作用以及随后的Aβ产生。据报道,低密度脂蛋白受体(LDLR)家族的各种成员在APP的运输和加工中起着作用,并且是AD中的重要危险因素。我们最近表征了称为LRLR相关蛋白10(LRP10)的LDLR家族的一个独特成员,该成员在反高尔基网络(TGN),质膜(PM)和内体之间穿梭。在这里,我们调查了LRP10是否参与APP细胞内运输和Aβ的产生。

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