{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:43:34Z","timestamp":1775018614042,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>MicroRNAs have been demonstrated as key regulators of gene expression in the etiology of a range of diseases including Alzheimer\u2019s disease (AD). Recently, we identified miR-483-5p as the most upregulated miRNA amongst a panel of miRNAs in blood plasma specific to prodromal, early-stage Alzheimer\u2019s disease patients. Here, we investigated the functional role of miR-483-5p in AD pathology. Using TargetScan and miRTarBase, we identified the microtubule-associated protein MAPT, often referred to as TAU, and the extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), known to phosphorylate TAU, as predicted direct targets of miR-483-5p. Employing several functional assays, we found that miR-483-5p regulates ERK1 and ERK2 at both mRNA and protein levels, resulting in lower levels of phosphorylated forms of both kinases. Moreover, miR-483-5p-mediated repression of ERK1\/2 resulted in reduced phosphorylation of TAU protein at epitopes associated with TAU neurofibrillary pathology in AD. These results indicate that upregulation of miR-483-5p can decrease phosphorylation of TAU via ERK pathway, representing a compensatory neuroprotective mechanism in AD pathology. This miR-483-5p\/ERK1\/TAU axis thus represents a novel target for intervention in AD.<\/jats:p>","DOI":"10.3390\/ijms22073653","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T07:23:17Z","timestamp":1617261797000},"page":"3653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Candidate Alzheimer\u2019s Disease Biomarker miR-483-5p Lowers TAU Phosphorylation by Direct ERK1\/2 Repression"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8132-491X","authenticated-orcid":false,"given":"Siranjeevi","family":"Nagaraj","sequence":"first","affiliation":[{"name":"Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7800-873X","authenticated-orcid":false,"given":"Andrew","family":"Want","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland"}]},{"given":"Katarzyna","family":"Laskowska-Kaszub","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland"}]},{"given":"Aleksandra","family":"Fesiuk","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland"},{"name":"i3S, Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Sara","family":"Vaz","sequence":"additional","affiliation":[{"name":"i3S, Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8741-0744","authenticated-orcid":false,"given":"Elsa","family":"Logarinho","sequence":"additional","affiliation":[{"name":"i3S, Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"Aging and Aneuploidy Laboratory, IBMC, Institute of Molecular and Cellular Biology, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4525-2004","authenticated-orcid":false,"given":"Urszula","family":"Wojda","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13195-016-0188-8","article-title":"Recent global trends in the prevalence and incidence of dementia, and survival with dementia","volume":"8","author":"Prince","year":"2016","journal-title":"Alzheimers Res. 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