2026-05-17T00:18:31Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/172282024-09-28T02:51:21Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617

00925njm 22002777a 4500 dc Coronel Lopez, Raquel author Rosca, Andreea author González-Sastre, Rosa author Mateos-Martínez, Patricia author Gallego, Marta Ines author Liste-Noya, Isabel author López-Alonso, Victoria author 2023 Numerous studies have focused on the pathophysiological role of amyloid precursor protein (APP) in Alzheimer's disease (AD), being the aggregation of β-amyloid (Aβ) peptide a central event. However, many authors consider that alterations in physiological functions of APP are likely to play a key role in AD pathogenesis. APP is a glycoprotein expressed ubiquitously in a wide variety of tissues, being especially abundant in the brain. The APP expression is detected at early stages of nervous system development, as well as in adult brain, suggesting that this protein plays a key and important role at various stages of life. Previous studies in our laboratory revealed that APP playing an important role on differentiation of human neural stem cells (hNSCs), favoring glial differentiation (gliogenesis), and preventing the differentiation of them towards neuronal phenotype (neurogenesis). In that case, we proposed to the APP/AICD/GSK-3β system as a possible molecular mechanism involved in the observed effects. However, given the multifunctionality of APP, we think that other molecular mechanisms could also be implicated. In the present study, we have evaluated the effects of APP overexpression in hNSCs at a global level by a transcriptomic analysis using the massive RNA sequencing (RNA-seq) technology. Specifically, we have focused on differentially expressed genes (DEGs) that are related to neuronal and glial differentiation processes, as well as on groups of DEGs associated with different signaling pathways, to find a possible interaction between them and APP. Our data indicate a differential expression in genes related to gliogenesis and neurogenesis processes, as well as in the pathways of Notch signaling, Wnt signaling, PI3K-AKT signaling, and JAK-STAT signaling, among other. The knowledge of physiological functions of APP, as well as the possible signaling pathways that could be implicated, are essential to advance the understanding of the pathogenesis of AD. IBRO Neuroscience Reports. 2023;15(S1):S172. 10.1016/j.ibneur.2023.08.251 2667-2421 IBRO Neuroscience Reports http://hdl.handle.net/20.500.12105/17228 RNA-seq Alzheimer’s disease Amyloid protein Human neural stem cells RNA-SEQ analysis reveals the implication of Amyloid Precursor Protein (APP) in cell fate specification of human neural Stem Cells by several Signaling Pathways. IBRO Neuroscience Reports