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DXY inhibits H-PAS activity to treat multiple sclerosis

Yuxin Zhuang;Fen Yang;Wei Qiu;Jianlin Wu;Meixian Liu;Kawai Lei;Liang Liu;Ting Li

  Multiple sclerosis(MS) is a central nervous system(CNS) autoimmune disease caused by inflammation and demyelination.In the current study, we haveidentifiedDXY,a compound derived from Chinese medicinal herb,effectively ameliorated EAE symptoms via selectively suppressing Th17 in vivo.After conducting metabolomics study, we foundthat PA production was decreased in Th17 treated with DXY and upregulated in MS patients and experimental autoimmune encephalomyelitis(EAE) mouse model. Fueling PS could further intensively and selectively up-regulate Th17 differentiation in vitro,suggesting that consumption of PS promoted Th17 differentiation. Importantly, the symptoms of EAE micein addition of PAare much more severity than vehicle treatment. We found that PA production is synthesized by H-PAS rather than L-PAS in T lymphocytes. DXY covalently bound to H-PAS rather than L-PAS to inhibit PA production, and in turn suppressed Th17 differentiation as well as EAE progression. Collectively, our identified a novelH-PAS inhibitor with inhibitory effect on Th17 differentiation and inhibition of H-PAS activity potential to be developed as a novel strategy to treat MS.……