{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:48:25Z","timestamp":1783529305165,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Science and Innovation","award":["RTI2018-101663-B-100"],"award-info":[{"award-number":["RTI2018-101663-B-100"]}]},{"name":"Spanish Ministry of Science and Innovation","award":["PID2021-126715OB-I00"],"award-info":[{"award-number":["PID2021-126715OB-I00"]}]},{"name":"MCIN\/AEI\/10.13039\/501100011033","award":["RTI2018-101663-B-100"],"award-info":[{"award-number":["RTI2018-101663-B-100"]}]},{"name":"MCIN\/AEI\/10.13039\/501100011033","award":["PID2021-126715OB-I00"],"award-info":[{"award-number":["PID2021-126715OB-I00"]}]},{"name":"ERDF A way of making Europe","award":["RTI2018-101663-B-100"],"award-info":[{"award-number":["RTI2018-101663-B-100"]}]},{"name":"ERDF A way of making Europe","award":["PID2021-126715OB-I00"],"award-info":[{"award-number":["PID2021-126715OB-I00"]}]},{"name":"FPU predoctoral contract from Universidad de Alcal\u00e1","award":["RTI2018-101663-B-100"],"award-info":[{"award-number":["RTI2018-101663-B-100"]}]},{"name":"FPU predoctoral contract from Universidad de Alcal\u00e1","award":["PID2021-126715OB-I00"],"award-info":[{"award-number":["PID2021-126715OB-I00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyloid precursor protein (APP) has been widely studied due to its association with Alzheimer\u2019s disease (AD). However, the physiological functions of APP are still largely unexplored. APP is a transmembrane glycoprotein whose expression in humans is abundant in the central nervous system. Specifically, several studies have revealed the high expression of APP during brain development. Previous studies in our laboratory revealed that a transient increase in APP expression induces early cell cycle exit of human neural stem cells (hNSCs) and directs their differentiation towards glial cells (gliogenesis) while decreasing their differentiation towards neurons (neurogenesis). In the present study, we have evaluated the intrinsic cellular effects of APP down-expression (using siRNA) on cell death, cell proliferation, and cell fate specification of hNSCs. Our data indicate that APP silencing causes cellular effects opposite to those obtained in previous APP overexpression assays, inducing cell proliferation in hNS1 cells (a model line of hNSCs) and favoring neurogenesis instead of gliogenesis in these cells. In addition, we have analyzed the gene and protein expression levels of \u03b2-Catenin as a possible molecule involved in these cellular effects. These data could help to understand the biological role of APP, which is necessary to deepen the knowledge of AD.<\/jats:p>","DOI":"10.3390\/ijms241914635","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T07:38:46Z","timestamp":1695800326000},"page":"14635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Low Levels of Amyloid Precursor Protein (APP) Promote Neurogenesis and Decrease Gliogenesis in Human Neural Stem Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1156-2151","authenticated-orcid":false,"given":"Raquel","family":"Coronel","sequence":"first","affiliation":[{"name":"Unidad de Regeneraci\u00f3n Neural, Unidad Funcional de Investigaci\u00f3n de Enfermedades Cr\u00f3nicas, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"},{"name":"Departamento de Biolog\u00eda de Sistemas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8129-8352","authenticated-orcid":false,"given":"Victoria","family":"L\u00f3pez-Alonso","sequence":"additional","affiliation":[{"name":"Unidad de Biolog\u00eda Computacional, Unidad Funcional de Investigaci\u00f3n de Enfermedades Cr\u00f3nicas, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0143-2553","authenticated-orcid":false,"given":"Marta I.","family":"Gallego","sequence":"additional","affiliation":[{"name":"Unidad de Histolog\u00eda y Patolog\u00eda Mamaria, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Liste","sequence":"additional","affiliation":[{"name":"Unidad de Regeneraci\u00f3n Neural, Unidad Funcional de Investigaci\u00f3n de Enfermedades Cr\u00f3nicas, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer\u2019s disease","volume":"25","author":"Lane","year":"2018","journal-title":"Eur. 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