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These properties led us to test the effects of <jats:styled-content style=\"fixed-case\">LKE<\/jats:styled-content> in experimental autoimmune encephalomyelitis (<jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content>), a commonly used mouse model of multiple sclerosis. Female C57Bl\/6 mice were immunized with myelin oligodendrocyte glycoprotein peptide 35\u201355 to develop a chronic disease. <jats:styled-content style=\"fixed-case\">LKE<\/jats:styled-content> was provided in the chow at 100\u00a0ppm, <jats:italic>ad\u00a0libitum<\/jats:italic> beginning when the mice reached moderate clinical signs. Over the following 4\u00a0weeks the <jats:styled-content style=\"fixed-case\">LKE<\/jats:styled-content>\u2010treated mice showed a significant reduction in clinical signs compared to vehicle\u2010treated mice. <jats:styled-content style=\"fixed-case\">LKE<\/jats:styled-content> dose dependently reduced <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b3 production from splenic T cells, but had no effect on <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017 production suggesting protective effects were mediated within the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>. Electron microscopy revealed that, compared to sham mice, <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> mice had significant neurodegeneration in both the optic nerve and spinal cord, which was reduced in the <jats:styled-content style=\"fixed-case\">LKE<\/jats:styled-content>\u2010treated mice. In contrast only minimal disruption of myelin was observed at this time point. In the optic nerve, measurements of axon caliber and myelin thickness showed little changes between sham and <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> mice, however, treatment with <jats:styled-content style=\"fixed-case\">LKE<\/jats:styled-content> increased the percentage of axons with thicker myelin and with larger axon calibers. In the spinal cord, only smaller effects of <jats:styled-content style=\"fixed-case\">LKE<\/jats:styled-content> on myelin thickness were observed. The effects of <jats:styled-content style=\"fixed-case\">LKE<\/jats:styled-content> were associated with a reduced relative level of phosphorylated <jats:styled-content style=\"fixed-case\">CRMP<\/jats:styled-content>2 to <jats:styled-content style=\"fixed-case\">CRMP<\/jats:styled-content>2. Together, these results demonstrate that <jats:styled-content style=\"fixed-case\">LKE<\/jats:styled-content> reduces neurodegeneration in a chronic <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> model of <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>, which could have translation potential for treatment of progressive forms of <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13114-fig-0011-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nOnly few drugs have been shown to reduce neurodegeneration in multiple sclerosis (MS). We report that LKE (lanthionine ketimine ethyl\u2010ester, a derivative of the amino acid lanthionine) reduced clinical signs in a mouse model of chronic MS, and also reduced neurodegeneration and axonal damage in the spinal cord and optic nerve (shown in the graphic). These effects were associated with changes in levels and phosphorylation state of CRMP2 (collapsin response mediator protein 2), which has known actions on axon growth. These findings suggest that LKE may be a candidate for testing in progressive forms of MS.\n<\/jats:p>","DOI":"10.1111\/jnc.13114","type":"journal-article","created":{"date-parts":[[2015,4,6]],"date-time":"2015-04-06T07:51:31Z","timestamp":1428306691000},"page":"302-314","source":"Crossref","is-referenced-by-count":40,"title":["Lanthionine ketimine ester provides benefit in a mouse model of multiple sclerosis"],"prefix":"10.1111","volume":"134","author":[{"given":"Jeffrey L.","family":"Dupree","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Polak","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Hensley","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Toledo College of Medicine Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Pelligrino","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas L.","family":"Feinstein","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Illinois at Chicago Chicago Illinois USA"},{"name":"Department of Veterans Affairs Jesse Brown VA Medical Center Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2011.06.003"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.01.006"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12664"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21307"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514544537"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-9281-5_28"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1991.tb16365.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80093-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400412200"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq237"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.2098"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006908013972"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2010.09.005"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.02.006"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10206"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2012.07742.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610797200"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)91418-R"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022083809994"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2011.10.011"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/376509a0"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(81)90042-3"},{"issue":"1","key":"e_1_2_7_24_1","first-page":"281","article-title":"Maintenance of myelinated fibre g ratio in acute experimental allergic encephalomyelitis","volume":"114","author":"Guy J.","year":"1991","journal-title":"Brain"},{"key":"e_1_2_7_25_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.freeradbiomed.2014.10.581","article-title":"Alternative functions of the brain transsulfuration pathway represent an underappreciated aspect of brain redox biochemistry with significant potential for therapeutic engagement","volume":"78","author":"Hensley K.","year":"2014","journal-title":"Free Radic. 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