The production of neurotoxic amyloid-β peptides (Aβ) is central to the initiation and progression of Alzheimer's disease (AD) and involves sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. APP and the secretases are transmembrane proteins and their co-localisation in the same membrane-bound sub-compartment is necessary for APP cleavage. The intracellular trafficking of APP and the β-secretase, BACE1, is critical in regulating APP processing and Aβ production and has been studied in several cellular systems. Here, we summarise the intracellular distribution and transport of APP and its secretases, and the intracellular location for APP cleavage in non-polarised cells and neuronal models. In addition, we review recent advances on the potential impact of familial AD mutations on APP trafficking and processing. This is critical information in understanding the molecular mechanisms of AD progression and in supporting the development of novel strategies for clinical treatment.

中文翻译：

---

淀粉样蛋白前体蛋白运输和加工的细胞生物学进展：家族性阿尔茨海默病突变的影响。


神经毒性淀粉样蛋白β肽 （Aβ） 的产生是阿尔茨海默病 （AD） 发生和发展的核心，涉及 β 和 γ 分泌酶对淀粉样蛋白前体蛋白 （APP） 的连续切割。APP 和分泌酶是跨膜蛋白，它们共定位于同一个膜结合的子区室是 APP 切割所必需的。APP 和 β 分泌酶 BACE1 的细胞内运输在调节 APP 加工和 Aβ 产生中至关重要，并且已在多个细胞系统中进行了研究。在这里，我们总结了 APP 及其分泌酶的细胞内分布和转运，以及非极化细胞和神经元模型中 APP 切割的细胞内位置。此外，我们回顾了家族性 AD 突变对 APP 贩运和加工的潜在影响的最新进展。这是了解 AD 进展的分子机制和支持临床治疗新策略开发的关键信息。