A novel fatty acid-binding protein 5 and 7 inhibitor ameliorates oligodendrocyte injury in multiple sclerosis mouse models

• DOI: 10.1016/j.ebiom.2021.103582
• Publication Date: 2021-10-06T01:35:15Z
• Authors: An Cheng; Wenbin Jia; Ichiro Kawahata; Kohji Fukunaga
• Keywords: Myelin oligodendrocyte glycoprotein

Multiple sclerosis (MS) is an autoimmune disease characterised by the demyelination of mature oligodendrocytes in central nervous system. Recently, several studies have indicated vital roles fatty acid-binding proteins (FABPs) 5 and 7 regulating immune response.We assessed a novel FABP5/FABP7 inhibitor, FABP ligand 6 (MF 6), as potential therapeutic for MS therapy. In vivo, we established MOG35-55-administered experimental encephalomyelitis (EAE) mice mouse model, followed prophylactic symptomatic treatment with MF 6. The effect was determined using behavioural biochemical analyses. vitro, effects on astrocytes were examined both astrocyte primary culture KG-1C cell lines.Prophylactic therapy reduced myelin loss clinical EAE symptoms. Furthermore, oxidative stress levels GFAP-positive ionised calcium-binding adaptor protein-1-positive cells spinal cord 6-treated mice. addition, attenuated lipopolysaccharide-stimulated interleukin-1β tumour necrosis factor-α accumulation culture. Moreover, powerful protective function mitochondria via FABP5 inhibition.MF potent inhibitor FABP7; targeted inhibition two may confer oligodendrocyte protection.This work supported Strategic Research Program Brain Sciences from Japan Agency Medical Development (JP17dm0107071, JP18dm0107071, JP19dm0107071, JP20dm0107071).