{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T20:27:06Z","timestamp":1782419226033,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-096386-B-I00"],"award-info":[{"award-number":["RTI2018-096386-B-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015496","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas","doi-asserted-by":"publisher","award":["CB06\/05\/1105"],"award-info":[{"award-number":["CB06\/05\/1105"]}],"id":[{"id":"10.13039\/501100015496","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TERCEL","award":["RD16\/0011\/0014"],"award-info":[{"award-number":["RD16\/0011\/0014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Loss of motor neurons (MNs) after spinal root injury is a drawback limiting the recovery after palliative surgery by nerve or muscle transfers. Research based on preventing MN death is a hallmark to improve the perspectives of recovery following severe nerve injuries. Sigma-1 receptor (Sig-1R) is a protein highly expressed in MNs, proposed as neuroprotective target for ameliorating MN degenerative conditions. Here, we used a model of L4\u2013L5 rhizotomy in adult mice to induce MN degeneration and to evaluate the neuroprotective role of Sig-1R ligands (PRE-084, SA4503 and BD1063). Lumbar spinal cord was collected at 7, 14, 28 and 42 days post-injury (dpi) for immunohistochemistry, immunofluorescence and Western blot analyses. This proximal axotomy at the immediate postganglionic level resulted in significant death, up to 40% of spinal MNs at 42 days after injury and showed markedly increased glial reactivity. Sig-1R ligands PRE-084, SA4503 and BD1063 reduced MN loss by about 20%, associated to modulation of endoplasmic reticulum stress markers IRE1\u03b1 and XBP1. These pathways are Sig-1R specific since they were not produced in Sig-1R knockout mice. These findings suggest that Sig-1R is a promising target for the treatment of MN cell death after neural injuries.<\/jats:p>","DOI":"10.3390\/ijms22136956","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T11:45:40Z","timestamp":1624880740000},"page":"6956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Neuroprotective Effects of Sigma 1 Receptor Ligands on Motoneuron Death after Spinal Root Injury in Mice"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0028-570X","authenticated-orcid":false,"given":"N\u00faria","family":"Gaja-Capdevila","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona, 01893 Bellaterra, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5359-7598","authenticated-orcid":false,"given":"Neus","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona, 01893 Bellaterra, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zamanillo","sequence":"additional","affiliation":[{"name":"Welab, Parc Cient\u00edfic Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Miguel","family":"Vela","sequence":"additional","affiliation":[{"name":"Welab, Parc Cient\u00edfic Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Merlos","sequence":"additional","affiliation":[{"name":"Welab, Parc Cient\u00edfic Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9849-902X","authenticated-orcid":false,"given":"Xavier","family":"Navarro","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona, 01893 Bellaterra, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain"},{"name":"Institut Guttmann Hospital de Neurorehabilitaci\u00f3, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Herrando-Grabulosa","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona, 01893 Bellaterra, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.hcl.2015.12.001","article-title":"Nerve Regeneration. 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