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By employing an in\u00a0vitro system recapitulating the inflammatory environment of MS lesion, we show that when SF3B2 levels are downregulated, cell viability and axon integrity are preserved in cortical neurons against inflammatory toxicity. Notably, knockdown of SF3B2 suppresses the expression of injury\u2010response and necroptosis genes and prevents activation of Sterile Alpha and TIR Motif Containing 1 (Sarm1), a key enzyme that mediates programmed axon degeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Together, these findings suggest that the downregulation of SF3B2 is a novel potential therapeutic target to prevent secondary neurodegeneration in MS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51717","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T16:23:00Z","timestamp":1672158180000},"page":"246-265","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Downregulation of <scp>SF3B2<\/scp> protects <scp>CNS<\/scp> neurons in models of multiple sclerosis"],"prefix":"10.1002","volume":"10","author":[{"given":"Ye 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