{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T21:45:36Z","timestamp":1776548736437,"version":"3.51.2"},"reference-count":90,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["JPco-fuND\/0003\/2015"],"award-info":[{"award-number":["JPco-fuND\/0003\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MED-NEU\/31395\/2017"],"award-info":[{"award-number":["PTDC\/MED-NEU\/31395\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neuronal miRNA dysregulation may have a role in the pathophysiology of Alzheimer\u2019s disease (AD). miRNA(miR)-124 is largely abundant and a critical player in many neuronal functions. However, the lack of models reliably recapitulating AD pathophysiology hampers our understanding of miR-124\u2019s role in the disease. Using the classical human SH-SY5Y-APP695 Swedish neuroblastoma cells (SH-SWE) and the PSEN1 mutant iPSC-derived neurons (iNEU-PSEN), we observed a sustained upregulation of miR-124\/miR-125b\/miR-21, but only miR-124 was consistently shuttled into their exosomes. The miR-124 mimic reduced APP gene expression in both AD models. While miR-124 mimic in SH-SWE neurons led to neurite outgrowth, mitochondria activation and small A\u03b2 oligomer reduction, in iNEU-PSEN cells it diminished Tau phosphorylation, whereas miR-124 inhibitor decreased dendritic spine density. In exosomes, cellular transfection with the mimic predominantly downregulated miR-125b\/miR-21\/miR-146a\/miR-155. The miR-124 inhibitor upregulated miR-146a in the two experimental cell models, while it led to distinct miRNA signatures in cells and exosomes. In sum, though miR-124 function may be dependent on the neuronal AD model, data indicate that keeping miR-124 level strictly controlled is crucial for proper neuronal function. Moreover, the iNEU-PSEN cellular model stands out as a useful tool for AD mechanistic studies and perhaps for the development of personalized therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cells10092424","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T23:34:11Z","timestamp":1631662451000},"page":"2424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Neuronal Dynamics and miRNA Signaling Differ between SH-SY5Y APPSwe and PSEN1 Mutant iPSC-Derived AD Models upon Modulation with miR-124 Mimic and Inhibitor"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-5362","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Garcia","sequence":"first","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Laboratory, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"given":"Sara","family":"Pinto","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Laboratory, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9999-5885","authenticated-orcid":false,"given":"Mar","family":"Cunha","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Laboratory, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-9519","authenticated-orcid":false,"given":"Adelaide","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"Central Nervous System, Blood and Peripheral Inflammation, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"given":"Jari","family":"Koistinaho","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70211 Kuopio, Finland"},{"name":"Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, FI-00014 Helsinki, Finland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3024-9777","authenticated-orcid":false,"given":"Dora","family":"Brites","sequence":"additional","affiliation":[{"name":"Neuroinflammation, Signaling and Neuroregeneration Laboratory, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0960-9822(02)00809-6","article-title":"Identification of tissue-specific microRNAs from mouse","volume":"12","author":"Rauhut","year":"2002","journal-title":"Curr. 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