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Comment
. 2018 Jun;28(6):613-615.
doi: 10.1038/s41422-018-0045-3.

Dimethyl fumarate: targeting glycolysis to treat MS

Stefano Angiari  1 , Luke A O'Neill  2
Affiliations
Comment

Dimethyl fumarate: targeting glycolysis to treat MS

Stefano Angiari et al. Cell Res. 2018 Jun.
No abstract available

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Figures

Fig. 1
Fig. 1
GAPDH is a target for dimethyl fumarate. Following activation, innate and adaptive immune cells increase glucose uptake to fuel aerobic glycolysis, an essential step for their activation and effector functions, and GAPDH represents a rate-limiting enzyme in this pathway. Engagement of glycolysis favors the generation of pro-inflammatory immune cell subsets such as M1-polarized macrophages, Th1 and Th17 cells. DMF and MMF both alter the functionality of GAPDH, by inducing succination of Cys-152 in the enzyme active site. This modification inactivates GAPDH, causing a block in glycolysis, an increase in OXPHOS, the development of anti-inflammatory immune cell subsets such as Tregs and M2-polarized macrophages, and an overall inhibition of the inflammatory response. Abbreviations not present in the main text: TCR T-cell receptor, Cys cysteine, 2SC S-(2-succino)cysteine, Mϕ macrophage
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