Lanthionine ketimine ester provides benefit in a mouse model of multiple sclerosis.

摘要: Lanthionine ketimine (LK) is a natural sulfur amino acid metabolite which binds to collapsin response mediator protein-2 (CRMP2), an abundant brain protein that interacts with multiple partners regulate microtubule dynamics, neurite growth and retraction, axonal transport, neurotransmitter release. LK ethyl-ester (LKE) cell-permeable synthetic derivative promotes neurogenesis, suppresses nitric oxide production from microglia, reduces neurotoxicity of microglia-conditioned medium. These properties led us test the effects LKE in experimental autoimmune encephalomyelitis (EAE), commonly used mouse model sclerosis. Female C57Bl/6 mice were immunized myelin oligodendrocyte glycoprotein peptide 35–55 develop chronic disease. was provided chow at 100 ppm, ad libitum beginning when reached moderate clinical signs. Over following 4 weeks LKE-treated showed significant reduction signs compared vehicle-treated mice. dose dependently reduced IFNγ splenic T cells, but had no effect on IL-17 suggesting protective mediated within CNS. Electron microscopy revealed that, sham mice, EAE neurodegeneration both optic nerve spinal cord, In contrast only minimal disruption observed this time point. nerve, measurements axon caliber thickness little changes between however, treatment increased percentage axons thicker larger calibers. smaller observed. The associated relative level phosphorylated CRMP2 CRMP2. Together, these results demonstrate MS, could have translation potential for progressive forms MS. Only few drugs been shown reduce sclerosis (MS). We report (lanthionine ethyl-ester, lanthionine) also damage cord (shown graphic). levels phosphorylation state (collapsin 2), has known actions growth. findings suggest may be candidate testing