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A novel fatty acid-binding protein 5 and 7 inhibitor ameliorates oligodendrocyte injury in multiple sclerosis mouse models
- Source :
- EBioMedicine, Vol 72, Iss, Pp 103582-(2021), EBioMedicine
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- 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-1β and TNF-α 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. Funding Information: We thank the Uehara Memorial Foundation for their financial support. This work was supported in part by the Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and Development (JP17dm0107071, JP18dm0107071, JP19dm0107071, and JP20dm0107071, awarded to K.F. Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: Ethical approval was obtained from the Institutional Animal Care and Use Committee of the Tohoku University Environmental and Safety Committee (2019PhLM0-021 and 2019PhA-024).
- Subjects :
- Medicine (General)
Encephalomyelitis, Autoimmune, Experimental
Research paper
Central nervous system
Pharmacology
General Biochemistry, Genetics and Molecular Biology
Multiple sclerosis
Mice
Immune system
R5-920
Animals
Humans
Medicine
Cells, Cultured
Autoimmune disease
Microglia
business.industry
Experimental autoimmune encephalomyelitis
General Medicine
FABP7
medicine.disease
Fatty acid-binding proteins
Oligodendrocyte
Neoplasm Proteins
Mitochondria
Mice, Inbred C57BL
Disease Models, Animal
Oligodendroglia
medicine.anatomical_structure
Astrocytes
Female
Fatty Acid-Binding Protein 7
business
Astrocyte
Subjects
Details
- Language :
- English
- ISSN :
- 23523964
- Volume :
- 72
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....12b4fd182555f80dbca9ea0f9091c587