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Divalent Metal Transporter1, a major iron importer in cells, is stimulated by signaling of Dexras1, a small G protein member of the Ras family. Dexras1 is activated by S-nitrosylation by nitric oxide (NO) produced by either inducible nitric oxide synthase in activated microglia\/macrophages or neuronal nitric oxide synthase in neurons. Here we show Dexras1 exacerbates oxidative stress-induced neurodegeneration in experimental optic neuritis, an inflammatory demyelinating optic nerve condition that occurs in MS and EAE. Dexras1 deletion, as well as treatment with the iron chelator deferiprone, preserves vision and attenuates retinal ganglion cell (RGC) and axonal loss during EAE optic neuritis. These results suggest that iron entry triggered by NO-activated Dexras1 signaling is a potential mechanism of neuronal death in experimental optic neuritis. The current data suggest modulation of Dexras1 signaling and iron chelation are potential novel treatment strategies for optic neuritis and MS, and possibly other optic neuropathies as well.<\/jats:p>","DOI":"10.1038\/s41598-019-48087-3","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T10:03:15Z","timestamp":1565604195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Dexras1 Deletion and Iron Chelation Promote Neuroprotection in Experimental Optic Neuritis"],"prefix":"10.1038","volume":"9","author":[{"given":"Reas S.","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5569-7261","authenticated-orcid":false,"given":"Kimberly","family":"Dine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua L.","family":"Dunaief","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangwon F.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth S.","family":"Shindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,8,12]]},"reference":[{"key":"48087_CR1","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1056\/NEJM199202273260901","volume":"326","author":"RW Beck","year":"1992","unstructured":"Beck, R. 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