The α,β-unsaturated moiety-bearing Nrf2 activator dimethyl fumarate has been approved by the FDA for the management of multiple sclerosis, while several other multi-target drug candidates are in clinical trials for various indications, including curcumin (impaired glucose tolerance and insulin resistance; NCT01052025), licochalcone A (squamous cell carcinoma; NCT03292822) and parthenolide (cancer; NCT00133341) (Figure 1) [7]. This evidence concerns the gene NFE2L2 and multiple sclerosis.