Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity

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Science  27 Apr 2018:
Vol. 360, Issue 6387, pp. 449-453
DOI: 10.1126/science.aan4665

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Immunometabolism as therapeutic target

Dimethyl fumarate (DMF) is an immunomodulatory compound used to treat multiple sclerosis and psoriasis whose mechanisms of action remain only partially understood. Kornberg et al. found that DMF and its metabolite, monomethyl fumarate, succinate the glycolytic enzyme GAPDH (see the Perspective by Matsushita and Pearce). After DMF treatment, GAPDH was inactivated, and aerobic glycolysis was down-regulated in both myeloid and lymphoid cells. This resulted in down-modulated immune responses because inflammatory immune-cell subsets require aerobic glycolysis. Thus, metabolism can serve as a viable therapeutic target in autoimmune disease.

Science, this issue p. 449; see also p. 377