DMF (Dimethyl Fumarate)

Dimethyl fumarate causes short-lived oxidative stress, which leads to increased levels and nuclear localization of the transcription factor nuclear factor erythroid 2-related factor 2 and a subsequent increase in glutathione synthesis and recycling in neuronal cells. ^[1] Dimethyl fumarate inhibits dendritic cell (DC) maturation by reducing inflammatory cytokine production (IL-12 and IL-6) and the expression of MHC class II, CD80, and CD86. Dimethyl fumarate impairs nuclear factor κB (NF-κB) signaling via reduced p65 nuclear translocalization and phosphorylation. Dimethyl fumarate inhibits maturation of DCs and subsequently Th1 and Th17 cell differentiation by suppression of both NF-κB and ERK1/2-MSK1 signaling. ^[2] Dimethyl fumarate inhibits TNF-alpha-induced nuclear entry of NF-kappaB in rat heart endothelial cells (RHEC). ^[3] Dimethyl fumarate, an immune modulator and inducer of the antioxidant response, suppresses HIV replication and neurotoxin release. Dimethyl fumarate attenuates CCL2-induced monocyte chemotaxis, suggesting that Dimethyl fumarate could decrease recruitment of activated monocytes to the CNS in response to inflammatory mediators. ^[4]

Dimethyl fumarate inhibits nuclear entry of NF-kappaB in RHEC and reduces myocardial infarct size after ischemia and reperfusion in rats in vivo. ^[3] Dimethyl fumarate oral administration is shown to upregulate mRNA and protein levels of Nrf2 and Nrf2-regulated cytoprotective genes, attenuate 6-OHDA induced striatal oxidative stress and inflammation in C57BL/6 mice. ^[5]