Ruprecht-Karls University Heidelberg, Institute of Pharmacy and Molecular Biotechnology, Bioinformatics and Functional Genomics, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
Goethe University Frankfurt, Institute of Clinical Neuroanatomy, Neuroscience Center, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Nat Rev Neurosci. 2017 May;18(5):281-298. doi: 10.1038/nrn.2017.29. Epub 2017 Mar 31.
Amyloid precursor protein (APP) gives rise to the amyloid-β peptide and thus has a key role in the pathogenesis of Alzheimer disease. By contrast, the physiological functions of APP and the closely related APP-like proteins (APLPs) remain less well understood. Studying these physiological functions has been challenging and has required a careful long-term strategy, including the analysis of different App-knockout and Aplp-knockout mice. In this Review, we summarize these findings, focusing on the in vivo roles of APP family members and their processing products for CNS development, synapse formation and function, brain injury and neuroprotection, as well as ageing. In addition, we discuss the implications of APP physiology for therapeutic approaches.
淀粉样前体蛋白（APP）生成淀粉样-β肽，因此在阿尔茨海默病的发病机制中起关键作用。相比之下，APP 和密切相关的 APP 样蛋白（APLPs）的生理功能仍知之甚少。研究这些生理功能具有挑战性，需要精心制定长期策略，包括分析不同的 App 敲除和 Aplp 敲除小鼠。在这篇综述中，我们总结了这些发现，重点介绍了 APP 家族成员及其加工产物在中枢神经系统发育、突触形成和功能、脑损伤和神经保护以及衰老中的体内作用。此外，我们还讨论了 APP 生理学对治疗方法的意义。
