{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:01:01Z","timestamp":1792789261907,"version":"4.5.0"},"reference-count":63,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Cariplo","award":["2022-0313"],"award-info":[{"award-number":["2022-0313"]}],"id":[{"id":"https:\/\/ror.org\/01gb56c55","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2022-0313"],"award-info":[{"award-number":["2022-0313"]}],"id":[{"id":"https:\/\/ror.org\/01gb56c55","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Oxaliplatin (OHP) is a key component of colorectal cancer chemotherapy, but OHP-induced peripheral neurotoxicity (OIPN) is a major dose-limiting adverse effect. OHP-related sodium-channel dysfunction could increase intracellular Na+ and sustain depolarization, conditions that may theoretically favor reverse-mode NCX activity, in which the exchanger promotes Ca2+ entry rather than Ca2+ extrusion. This study evaluated whether NCX2 targeting could reduce OHP-induced sensory neuron injury. Methods: Primary mouse dorsal root ganglion neurons were exposed to OHP, with or without SEA0400 (NCX modulator) pretreatment or siRNA-mediated NCX2 knockdown. Neuronal viability, neurite elongation, live-cell morphology, NCX2 fluorescence, and lipid droplet accumulation were quantified. Results: OHP reduced neuronal survival and neurite elongation and induced stress-related morphological changes and lipid droplet accumulation. NCX2-associated fluorescence varied by neuronal subtype, dose, and time. SEA0400 and partial NCX2 knockdown attenuated selected injury endpoints, mainly under low-dose conditions. Conclusions: These findings suggest that NCX2 may be involved in selected OHP-induced sensory neuron injury endpoints and support further investigation of NCX2 as a potential preventive target. However, reverse-mode NCX activity, Na+\/Ca2+ fluxes, NCX2 directionality, and translational relevance require direct validation.<\/jats:p>","DOI":"10.3390\/cancers18183024","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:59:03Z","timestamp":1789639143000},"page":"3024","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["NCX2 Targeting as a Neuroprotective Strategy Against Oxaliplatin-Induced Peripheral Neurotoxicity"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-1574","authenticated-orcid":false,"given":"Sara","family":"Di Girolamo","sequence":"first","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7506-9344","authenticated-orcid":false,"given":"Chiara","family":"Invernizzi","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, 20900 Monza, Italy"},{"name":"PhD Program in Neuroscience, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7624-0119","authenticated-orcid":false,"given":"Margherita Francesca","family":"Kraus","sequence":"additional","affiliation":[{"name":"S.C. Neuroscienze, Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle D\u2019Aosta, 10154 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1678-6357","authenticated-orcid":false,"given":"Elisa","family":"Ballarini","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Alessio","family":"Malacrida","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5876-6215","authenticated-orcid":false,"given":"Mario","family":"Mauri","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Virginia","family":"Rodriguez-Menendez","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Stephen N.","family":"Housley","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6106-6183","authenticated-orcid":false,"given":"Paola","family":"Alberti","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"iii\u2013ix, xi\u2013162","DOI":"10.3310\/hta12150","article-title":"The use of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer: Systematic review and economic evaluation","volume":"12","author":"Hind","year":"2008","journal-title":"Health Technol. 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