Curcumin suppressed inflammatory monocytes across the blood-brain barrier (BBB) in Experimental Autoimmune Encephalomyelitis (EAE) mice, suppressed the spread of microglia, and limited infiltration of other effector immune cells, resulting in a reduction in EAE morbidity from 100 to 30%. It was due to the immunomodulatory impact of curcumin-loaded high-density lipoprotein-mimicking peptide-phospholipid scaffold (Cur-HPPS) on inflammatory monocytes, which inhibited the activation of NF-κB and decreased the expression of adhesion-and migration-related molecules. This evidence concerns the gene NFKB1 and experimental autoimmune encephalomyelitis.