School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Hong Kong SAR, China.
Biochem Soc Trans. 2023 Aug 31;51(4):1647-1659. doi: 10.1042/BST20221527.
Amyloid precursor protein (APP) is a key molecule in the pathogenesis of Alzheimer's disease (AD) as the pathogenic amyloid-β peptide is derived from it. Two closely related APP family proteins (APPs) have also been identified in mammals. Current knowledge, including genetic analyses of gain- and loss-of-function mutants, highlights the importance of APPs in various physiological functions. Notably, APPs consist of multiple extracellular and intracellular protein-binding regions/domains. Protein-protein interactions are crucial for many cellular processes. In past decades, many APPs interactors have been identified which assist the revelation of the putative roles of APPs. Importantly, some of these interactors have been shown to influence several APPs-mediated neuronal processes which are found defective in AD and other neurodegenerative disorders. Studying APPs-interactor complexes would not only advance our understanding of the physiological roles of APPs but also provide further insights into the association of these processes to neurodegeneration, which may lead to the development of novel therapies. In this mini-review, we summarize the roles of APPs-interactor complexes in neurodevelopmental processes including neurogenesis, neurite outgrowth, axonal guidance and synaptogenesis.
淀粉样前体蛋白（APP）是阿尔茨海默病（AD）发病机制中的关键分子，因为致病淀粉样β肽来源于它。哺乳动物中也已鉴定出两种密切相关的 APP 家族蛋白（APPs）。目前的知识，包括对功能增益和功能丧失突变体的遗传分析，突出了 APPs 在各种生理功能中的重要性。值得注意的是，APPs 由多个细胞外和细胞内的蛋白质结合区域/结构域组成。蛋白质-蛋白质相互作用对于许多细胞过程至关重要。在过去的几十年中，已经鉴定出许多 APPs 相互作用蛋白，这些蛋白有助于揭示 APPs 的潜在作用。重要的是，其中一些相互作用蛋白已被证明会影响几种 APPs 介导的神经元过程，这些过程在 AD 和其他神经退行性疾病中被发现存在缺陷。研究 APPs-相互作用蛋白复合物不仅可以增进我们对 APPs 生理作用的理解，还可以进一步了解这些过程与神经退行性变的关联，这可能导致新疗法的开发。在这篇简要综述中，我们总结了 APPs-相互作用蛋白复合物在神经发育过程中的作用，包括神经发生、突起生长、轴突导向和突触发生。
