{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:27:48Z","timestamp":1773660468790,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III","award":["PI18\/00255"],"award-info":[{"award-number":["PI18\/00255"]}]},{"name":"Instituto de Salud Carlos III","award":["PI22\/01381"],"award-info":[{"award-number":["PI22\/01381"]}]},{"name":"Instituto de Salud Carlos III","award":["RICORS RD21\/0006\/0019"],"award-info":[{"award-number":["RICORS RD21\/0006\/0019"]}]},{"name":"European Regional Development Fund","award":["PI18\/00255"],"award-info":[{"award-number":["PI18\/00255"]}]},{"name":"European Regional Development Fund","award":["PI22\/01381"],"award-info":[{"award-number":["PI22\/01381"]}]},{"name":"European Regional Development Fund","award":["RICORS RD21\/0006\/0019"],"award-info":[{"award-number":["RICORS RD21\/0006\/0019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transient cerebral ischemia induces neuronal degeneration, followed in time by secondary delayed neuronal death that is strongly correlated with a permanent inhibition of protein synthesis in vulnerable brain regions, while protein translational rates are recovered in resistant areas. In the translation-regulation initiation step, the eukaryotic initiation factor (eIF) 4E is a key player regulated by its association with eIF4E-binding proteins (4E-BPs), mostly 4E-BP2 in brain tissue. In a previous work, we identified dihydropyrimidinase-related protein 2 (DRP2) as a 4E-BP2-interacting protein. Here, using a proteomic approach in a model of transient cerebral ischemia, a detailed study of DRP2 was performed in order to address the challenge of translation restoration in vulnerable regions. In this report, several DRP2 isoforms that have a specific interaction with both 4E-BP2 and eIF4E were identified, showing significant and opposite differences in this association, and being differentially detected in resistant and vulnerable regions in response to ischemia reperfusion. Our results provide the first evidence of DRP2 isoforms as potential regulators of the 4E-BP2\u2013eIF4E association that would have consequences in the delayed neuronal death under ischemic-reperfusion stress. The new knowledge reported here identifies DRP2 as a new target to promote neuronal survival after cerebral ischemia.<\/jats:p>","DOI":"10.3390\/ijms24098246","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T03:24:32Z","timestamp":1683257072000},"page":"8246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dihydropyrimidinase-Related Protein 2 Is a New Partner in the Binding between 4E-BP2 and eIF4E Related to Neuronal Death after Cerebral Ischemia"],"prefix":"10.3390","volume":"24","author":[{"given":"Emma","family":"Mart\u00ednez-Alonso","sequence":"first","affiliation":[{"name":"Department of Research, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"},{"name":"Proteomics Unit, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6408-2012","authenticated-orcid":false,"given":"Alejandro","family":"Escobar-Peso","sequence":"additional","affiliation":[{"name":"Department of Research, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Guerra-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Genetics, Physiology and Microbiology, Faculty of Biological Sciences, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0565-3954","authenticated-orcid":false,"given":"Marcel","family":"Roca","sequence":"additional","affiliation":[{"name":"Department of Research, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Masjuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"},{"name":"Department of Neurology, Facultad de Medicina, Universidad de Alcal\u00e1, 28871 Alcal\u00e1 de Henares, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Alc\u00e1zar","sequence":"additional","affiliation":[{"name":"Department of Research, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"},{"name":"Proteomics Unit, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1159\/000089370","article-title":"New goals in ischemic stroke therapy: The experimental approach--harmonizing science with practice","volume":"20","author":"Gutierrez","year":"2005","journal-title":"Cerebrovasc. 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