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SSRN Electronic Journal
CHENG, A;Jia, W;Kawahata, I;Fukunaga, K;
Multiple sclerosis (MS) is an autoimmune disease characterized by the demyelination of mature oligodendrocytes induced by dysregulated immune cells in the central nervous system (CNS). Recently, several studies have indicated the vital roles of fatty acid-binding proteins (FABPs) 5 and 7 in regulating the immune response via T cells and astrocytes, respectively, in experimental autoimmune encephalomyelitis (EAE) mice. We verified a novel FABP5/FABP7 inhibitor, FABP ligand 6 (MF 6), as a potential therapeutic drug for MS therapy in EAE mice. We demonstrated that MF 6 reduced myelin loss and clinical symptoms of EAE both pretreatment and posttreatment. Furthermore, we found decreased oxidative stress levels and decreased GFAP-positive and Iba-1-positive cells in the spinal cord of MF 6-treated mice. In astrocyte primary culture, MF 6 attenuated IL-1? and TNF-? accumulation, stimulated by LPS via inhibition of both FABP5 and FABP7. Moreover, MF 6 also suggested a powerful protective function of mitochondria in oligodendrocytes of EAE mice by blocking voltage-dependent anion channel-1-dependent mitochondrial macropore formation through FABP5 inhibition. Overall, we identified a novel FABP inhibitor, MF 6, which has potent therapeutic benefits for MS via both immune inhibition and oligodendrocyte protection.