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oai:repisalud.isciii.es:20.500.12105/88062025-02-27T14:35:31Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617

00925njm 22002777a 4500 dc Coronel Lopez, Raquel author Palmer, Charlotte author Bernabeu-Zornoza, Adela author Monteagudo, Maria author Rosca, Andreea author Zambrano, Alberto author Liste-Noya, Isabel author 2019-10 The pathological implication of amyloid precursor protein (APP) in Alzheimer's disease has been widely documented due to its involvement in the generation of amyloid-β peptide. However, the physiological functions of APP are still poorly understood. APP is considered a multimodal protein due to its role in a wide variety of processes, both in the embryo and in the adult brain. Specifically, APP seems to play a key role in the proliferation, differentiation and maturation of neural stem cells. In addition, APP can be processed through two canonical processing pathways, generating different functionally active fragments: soluble APP-α, soluble APP-β, amyloid-β peptide and the APP intracellular C-terminal domain. These fragments also appear to modulate various functions in neural stem cells, including the processes of proliferation, neurogenesis, gliogenesis or cell death. However, the molecular mechanisms involved in these effects are still unclear. In this review, we summarize the physiological functions of APP and its main proteolytic derivatives in neural stem cells, as well as the possible signaling pathways that could be implicated in these effects. The knowledge of these functions and signaling pathways involved in the onset or during the development of Alzheimer's disease is essential to advance the understanding of the pathogenesis of Alzheimer's disease, and in the search for potential therapeutic targets. Neural Regen Res. 2019 Oct;14(10):1661-1671. 10.4103/1673-5374.257511 1673-5374 Neural regeneration research 31169172 http://hdl.handle.net/20.500.12105/8806 APP APP intracellular domain Amyloid beta peptide Amyloid precursor protein Neural progenitor cells Neural stem cells Neurogenesis Signaling pathways Soluble APP alpha Soluble APP beta Physiological effects of amyloid precursor protein and its derivatives on neural stem cell biology and signaling pathways involved