{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:18:50Z","timestamp":1765484330874,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"publisher","award":["PID2020-112972RB-I00","ACCI2020","202032","P01NS097197","FPU18\/03969"],"award-info":[{"award-number":["PID2020-112972RB-I00","ACCI2020","202032","P01NS097197","FPU18\/03969"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CIBERER","award":["PID2020-112972RB-I00","ACCI2020","202032","P01NS097197","FPU18\/03969"],"award-info":[{"award-number":["PID2020-112972RB-I00","ACCI2020","202032","P01NS097197","FPU18\/03969"]}]},{"name":"la Fundaci\u00f3 La Marat\u00f3 TV3","award":["PID2020-112972RB-I00","ACCI2020","202032","P01NS097197","FPU18\/03969"],"award-info":[{"award-number":["PID2020-112972RB-I00","ACCI2020","202032","P01NS097197","FPU18\/03969"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["PID2020-112972RB-I00","ACCI2020","202032","P01NS097197","FPU18\/03969"],"award-info":[{"award-number":["PID2020-112972RB-I00","ACCI2020","202032","P01NS097197","FPU18\/03969"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish Ministry of Universities","award":["PID2020-112972RB-I00","ACCI2020","202032","P01NS097197","FPU18\/03969"],"award-info":[{"award-number":["PID2020-112972RB-I00","ACCI2020","202032","P01NS097197","FPU18\/03969"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lafora disease is a rare, fatal form of progressive myoclonus epilepsy characterized by continuous neurodegeneration with epileptic seizures, characterized by the intracellular accumulation of aberrant polyglucosan granules called Lafora bodies. Several works have provided numerous evidence of molecular and cellular alterations in neural tissue from experimental mouse models deficient in either laforin or malin, two proteins related to the disease. Oxidative stress, alterations in proteostasis, and deregulation of inflammatory signals are some of the molecular alterations underlying this condition in both KO animal models. Lafora bodies appear early in the animal\u2019s life, but many of the aforementioned molecular aberrant processes and the consequent neurological symptoms ensue only as animals age. Here, using small RNA-seq and quantitative PCR on brain extracts from laforin and malin KO male mice of different ages, we show that two different microRNA species, miR-155 and miR-146a, are overexpressed in an age-dependent manner. We also observed altered expression of putative target genes for each of the microRNAs studied in brain extracts. These results open the path for a detailed dissection of the molecular consequences of laforin and malin deficiency in brain tissue, as well as the potential role of miR-155 and miR-146a as specific biomarkers of disease progression in LD.<\/jats:p>","DOI":"10.3390\/ijms24021089","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T01:48:19Z","timestamp":1672969699000},"page":"1089","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Age-Related microRNA Overexpression in Lafora Disease Male Mice Provides Links between Neuroinflammation and Oxidative Stress"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7981-7157","authenticated-orcid":false,"given":"Carlos","family":"Rom\u00e1-Mateo","sequence":"first","affiliation":[{"name":"Department of Physiology, Facultat de Medicina i Odontologia, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"},{"name":"Fundaci\u00f3n Instituto de Investigaci\u00f3n Sanitaria INCLIVA, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2014ISCIII, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila","family":"Lorente-Pozo","sequence":"additional","affiliation":[{"name":"Neonatal Research Group, Health Research Institute La Fe, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5466-6380","authenticated-orcid":false,"given":"Luc\u00eda","family":"M\u00e1rquez-Thibaut","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Girona Dr. Josep Trueta (IDIBGI), Parc Hospitalari Mart\u00ed i Juli\u00e0 de Salt, 17190 Girona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8759-8794","authenticated-orcid":false,"given":"Mireia","family":"Moreno-Estell\u00e9s","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2014ISCIII, 46010 Valencia, Spain"},{"name":"Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Cient\u00edficas, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9903-511X","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Garc\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Physiology, Facultat de Medicina i Odontologia, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daym\u00e9","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"EpiDisease S.L. (Spin-off From the CIBER-ISCIII), Parc Cient\u00edfic de la Universitat de Val\u00e8ncia, 46980 Paterna, Spain"},{"name":"Novartis Institutes for BioMedical Research (NIBR), Novartis Campus, CH-4056 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos","family":"Lahuerta","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Cient\u00edficas, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Aguado","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2014ISCIII, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7547-7872","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Garc\u00eda-Gim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Physiology, Facultat de Medicina i Odontologia, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"},{"name":"Fundaci\u00f3n Instituto de Investigaci\u00f3n Sanitaria INCLIVA, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2014ISCIII, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-4103","authenticated-orcid":false,"given":"Pascual","family":"Sanz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2014ISCIII, 46010 Valencia, Spain"},{"name":"Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Cient\u00edficas, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3715-1980","authenticated-orcid":false,"given":"Federico V.","family":"Pallard\u00f3","sequence":"additional","affiliation":[{"name":"Department of Physiology, Facultat de Medicina i Odontologia, Universitat de Val\u00e8ncia, 46010 Valencia, Spain"},{"name":"Fundaci\u00f3n Instituto de Investigaci\u00f3n Sanitaria INCLIVA, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2014ISCIII, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8501","DOI":"10.1073\/pnas.0503285102","article-title":"Insights into Lafora Disease: Malin Is an E3 Ubiquitin Ligase That Ubiquitinates and Promotes the Degradation of Laforin","volume":"102","author":"Gentry","year":"2005","journal-title":"Proc. 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Treat"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1089\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:00:51Z","timestamp":1760119251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24021089"],"URL":"https:\/\/doi.org\/10.3390\/ijms24021089","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,1,6]]}}}