{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:10:42Z","timestamp":1791331842481,"version":"4.3.1"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Rio de Janeir","doi-asserted-by":"publisher","award":["201.174\/2022"],"award-info":[{"award-number":["201.174\/2022"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Rio de Janeir","doi-asserted-by":"publisher","award":["210.034\/2026"],"award-info":[{"award-number":["210.034\/2026"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","award":["88881.986154\/2024-01"],"award-info":[{"award-number":["88881.986154\/2024-01"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"award":["88881.986154\/2024-01"],"award-info":[{"award-number":["88881.986154\/2024-01"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Conselho Nacional Cient\u00edfico e Tecnol\u00f3gic","award":["309635\/2023-3"],"award-info":[{"award-number":["309635\/2023-3"]}]},{"name":"Conselho Nacional Cient\u00edfico e Tecnol\u00f3gic","award":["401780\/2023\u20136"],"award-info":[{"award-number":["401780\/2023\u20136"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glycation of superoxide dismutase 1 (SOD1) has been shown to modulate the cytosolic levels of phosphorylated TAR DNA-binding protein 43 (TDP-43), a hallmark of amyotrophic lateral sclerosis (ALS) pathology. In this study, we investigated the interaction between TDP-43 and SOD1 and assessed how methylglyoxal (MGO)-induced glycation and the ALS-associated G93A SOD1 mutation affect this interplay in H4 cells. MGO exposure reduced SOD1 activity and TDP-43 phosphorylation in cells expressing WT SOD1, but not in those expressing G93A SOD1. Both WT and mutant SOD1 interacted with TDP-43 in the nucleus and cytosol; however, cytosolic interactions were more prevalent in G93A-expressing cells. Although MGO did not significantly alter the overall interaction between TDP-43 and WT SOD1, it induced cytosolic inclusion formation at 0.4 mM, a concentration associated with reduced cell viability. These inclusions did not colocalize with stress granules, indicating alternative aggregation pathways. Treatment with cyclosporin A, which inhibits the phosphatase calcineurin, decreased both TDP-43\u2013WT SOD1 inclusions and cytosolic interactions between TDP-43 and G93A SOD1. Together, these findings suggest that SOD1 damage, induced by glycation or ALS-linked mutation, may affect TDP-43 phosphorylation status and promote its cytosolic mislocalization and aggregation, providing new insights into ALS-associated proteinopathy.<\/jats:p>","DOI":"10.3390\/ijms27083409","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:20:16Z","timestamp":1775816416000},"page":"3409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Modulation of the Crosstalk Between TDP-43 and SOD1"],"prefix":"10.3390","volume":"27","author":[{"given":"Gabriela D.","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Av. Athos da Silveira Ramos, 149, Rio de Janeiro 21941-909, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9166-5718","authenticated-orcid":false,"given":"Daniela D.","family":"Queiroz","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Av. Athos da Silveira Ramos, 149, Rio de Janeiro 21941-909, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4885-0931","authenticated-orcid":false,"given":"Jos\u00e9 R.","family":"Monteiro-Neto","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Av. Athos da Silveira Ramos, 149, Rio de Janeiro 21941-909, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Gerhardt","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8855-0582","authenticated-orcid":false,"given":"Gabriel F.","family":"de Souza","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Av. Athos da Silveira Ramos, 149, Rio de Janeiro 21941-909, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola C. S. C.","family":"Albino","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Av. Athos da Silveira Ramos, 149, Rio de Janeiro 21941-909, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0806-0062","authenticated-orcid":false,"given":"Luan H.","family":"Paranhos","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Av. Athos da Silveira Ramos, 149, Rio de Janeiro 21941-909, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago F.","family":"Outeiro","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"},{"name":"Max Planck Institute for Multidisciplinary Sciences, 37075 G\u00f6ttingen, Germany"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle Upon Tyne NE2 4HH, UK"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5842-2714","authenticated-orcid":false,"given":"Elis C. A.","family":"Eleutherio","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Av. Athos da Silveira Ramos, 149, Rio de Janeiro 21941-909, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic lateral sclerosis: A clinical review","volume":"27","author":"Masrori","year":"2020","journal-title":"Eur. J. 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