Figure 2.

Simplified pathway diagram showing selected proposed targets of dimethyl fumarate (DMF) and potential associated mechanisms at the molecular level. Solid arrows from DMF indicate literature evidence for direct binding to the target; dashed arrows indicate purported targets for which evidence of direct binding has not yet been provided (see text for detailed discussions). Thick dashed gray arrows indicate nuclear translocation events. Apart from Keap1, oligomeric states of proteins are depicted as monomeric for simplicity. Transcriptional co-regulators of Nrf2, NFκB, and CREB are omitted for clarity. Note that the mechanism of inhibition of NFκB signaling by activated HCA₂ (gray arrow) remains poorly understood but is likely indirect (Offermanns and Schwaninger, 2015).