{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:57:11Z","timestamp":1790567831713,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100024018","name":"Programa de Desarrollo de las Ciencias B\u00e1sicas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100024018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008725","name":"Agencia Nacional de Investigaci\u00f3n e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["FCE_3_2020_1_162440"],"award-info":[{"award-number":["FCE_3_2020_1_162440"]}],"id":[{"id":"10.13039\/100008725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002941","name":"Departamento de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas, Universidad de Santiago de Chile","doi-asserted-by":"publisher","award":["022401RP"],"award-info":[{"award-number":["022401RP"]}],"id":[{"id":"10.13039\/501100002941","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["EQM250063"],"award-info":[{"award-number":["EQM250063"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,9,28]]},"abstract":"<jats:p>\n                    Cannabidiol (CBD) and cannabigerol (CBG) are nonpsychotomimetic phytocannabinoids with neuroprotective properties. We have previously reported that CBD and CBG, but not their acidic forms, protect cerebellar granule neurons from rotenone\u2010induced toxicity. These effects were independent of canonical (i.e., cannabinoid 1 and 2\u2010receptors) and noncanonical cannabinoid targets (i.e., transient\u2010receptor potential vanilloid type 1 or peroxisome proliferator\u2010activated receptor), suggesting alternative mechanisms. The sigma\u20101 receptor (\u03c31R), a chaperone enriched at mitochondria\u2010associated membranes, regulates Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis, oxidative stress, and mitochondrial function, representing a neuroprotective target. In this study, we investigated the role of \u03c31R in\\ the neuroprotective actions of CBD and CBG using a rotenone\u2010induced neurotoxicity model in primary neuronal cultures. Pharmacological blockade of \u03c31R with NE\u2010100 abolished the neuroprotective effects of both cannabinoids, supporting a \u03c31R\u2010dependent mechanism. Consistently, molecular docking and molecular dynamics simulations using the human \u03c31R structure revealed stable binding of CBD and CBG within the ligand\u2010binding pocket, involving key residues for receptor recognition. According to the in vitro data, neutral forms showed higher predicted affinities than their acidic counterparts, while NE\u2010100 exhibited the strongest binding. These findings identify \u03c31R as a functionally relevant target for CBD and CBG, supporting their neuroprotective effects through modulation of \u03c31R\u2010mediated responses.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70510","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:21:16Z","timestamp":1790299276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Sigma\u20101 Receptor as a Novel Target in the Neuroprotective Effects of Cannabidiol and Cannabigerol Against Mitochondrial Damage in Cultured Cerebellar Granule Neurons"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1464-156X","authenticated-orcid":false,"given":"Victoria","family":"Oviedo\u2010Pino","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Ciencias Biol\u00f3gicas Universidad de Concepci\u00f3n  Concepci\u00f3n 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