Open AccessPhysiological effects of amyloid precursor protein and its derivatives on neural stem cell biology and signaling pathways involved
Author(s) -
Raquel Coronel,
Charlotte Palmer,
Adela Bernabeu-Zornoza,
María Jesús Monteagudo,
Andreea Rosca,
Alberto Zambrano,
Isabel Liste
Publication year - 2019
Publication title -
neural regeneration research/neural regeneration research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.257511
Subject(s) - neural stem cell , amyloid precursor protein , stem cell , microbiology and biotechnology , precursor cell , neuroscience , signal transduction , amyloid precursor protein secretase , biology , cell , computational biology , chemistry , bioinformatics , biochemistry , medicine , alzheimer's disease , pathology , disease
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.