論文 - 詳細
| RRC ID | 69919 |
|---|---|
| 著者 | Cheng A, Jia W, Kawahata I, Fukunaga K. |
| タイトル | A novel fatty acid-binding protein 5 and 7 inhibitor ameliorates oligodendrocyte injury in multiple sclerosis mouse models. |
| ジャーナル | EBioMedicine |
| Abstract |
BACKGROUND:Multiple sclerosis (MS) is an autoimmune disease characterised by the demyelination of mature oligodendrocytes in the central nervous system. Recently, several studies have indicated the vital roles of fatty acid-binding proteins (FABPs) 5 and 7 in regulating the immune response. METHODS:We assessed a novel FABP5/FABP7 inhibitor, FABP ligand 6 (MF 6), as a potential therapeutic for MS therapy. In vivo, we established MOG35-55-administered experimental autoimmune encephalomyelitis (EAE) mice as an MS mouse model, followed by prophylactic and symptomatic treatment with MF 6. The therapeutic effect of MF 6 was determined using behavioural and biochemical analyses. In vitro, MF 6 effects on astrocytes and oligodendrocytes were examined using both astrocyte primary culture and KG-1C cell lines. FINDINGS:Prophylactic and symptomatic MF 6 therapy reduced myelin loss and clinical EAE symptoms. Furthermore, oxidative stress levels and GFAP-positive and ionised calcium-binding adaptor protein-1-positive cells were reduced in the spinal cord of MF 6-treated mice. In addition, MF 6 attenuated lipopolysaccharide-stimulated interleukin-1β and tumour necrosis factor-α accumulation in primary astrocyte culture. Moreover, MF 6 indicated a powerful protective function for the mitochondria in the oligodendrocytes of EAE mice via FABP5 inhibition. INTERPRETATIONS:MF 6 is a potent inhibitor of FABP5 and FABP7; targeted inhibition of the two proteins may confer potential therapeutic effects in MS via immune inhibition and oligodendrocyte protection. FUNDING:This work was supported by the Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and Development (JP17dm0107071, JP18dm0107071, JP19dm0107071, and JP20dm0107071). |
| 巻・号 | 72 |
| ページ | 103582 |
| 公開日 | 2021-10-1 |
| DOI | 10.1016/j.ebiom.2021.103582 |
| PII | S2352-3964(21)00375-3 |
| PMID | 34624687 |
| PMC | PMC8502714 |
| MeSH | Animals Astrocytes / metabolism Cells, Cultured Disease Models, Animal Encephalomyelitis, Autoimmune, Experimental / metabolism Fatty Acid-Binding Protein 7 / metabolism* Fatty Acid-Binding Proteins / metabolism* Female Humans Mice Mice, Inbred C57BL Multiple Sclerosis / metabolism* Neoplasm Proteins / metabolism* Oligodendroglia / metabolism* |
| IF | 5.736 |
| リソース情報 | |
| ヒト・動物細胞 | KG-1-C(RCB0270) |