Dysregulation of methionine metabolism in multiple sclerosis.

We report a significant reduction in plasma methionine concentrations in relapse remitting multiple sclerosis (MS) patients compared to controls. In vivo studies demonstrate that changes in peripheral methionine levels in mice can regulate histone H3 methylation and expression of DNA methyltransferase 3A (DNMT3A) centrally, in the cerebral cortex. Therefore, we propose that decreases in circulating methionine represent one of the earliest manifestations of dysregulated methionine metabolism in MS with potential impacts on both histone H3 and DNA methylation in the central nervous system.