Table 1.

The operative mechanisms of action of MIF and D-DT in MS, Alzheimer disease and glioblastoma and potential therapeutic anti-MIF/D-DT drugs that could block their pathogenic effects

Disease	MIF mechanism of action	MIF targeting
Multiple sclerosis	• Induces leukocyte migration [52, 69] • Activation of macrophages, astrocytes and microglia [48, 63–67] • Promotes resistance of CD4( +) T cells to glucocorticoid treatment [68] • Increases pro-inflammatory cytokine secretion [52, 64]	• Partial MHC class II constructs [66–69, 169–176] • Ibudilast [52, 72, 161] • ISO-1 [70]
Alzheimer disease	• Secreted by microglia near Aβ plaques [77, 78] • Activation of astrocytes [79] • Induces neurotoxicity [77, 85]	• ISO-1 [81, 112, 145, 146] • Sulforaphane [120] • Ibudilast [103, 148] • mIR-608 [125] • 4-IPP [140]
Glioblastoma	• Induces cell cycle progression, tumor growth, blockage of apoptosis [108, 109, 131] • Induces angiogenesis and tumor spread [98] • Inhibition of NK and T cell anti-cancer cytotoxicity [99–103] • Promotes MDSCs and M2 macrophage polarization [99–103]	• ISO-1 [112, 145] • shRNA MIF inhibitor [119] • Monoclonal antibodies against MIF [118, 123, 145]