The expression of MAFG in mice is high compared to human (Data from public data bases
MAFG-driven astrocytes promote CNS inflammation. Wheeler MA, Clark IC, Tjon EC, Li Z, Zandee SEJ, Couturier CP, Watson BR, Scalisi G, Alkwai S, Rothhammer V, Rotem A, Heyman JA, Thaploo S, Sanmarco LM, Ragoussis J, Weitz DA, Petrecca K, Moffitt JR, Becher B, Antel JP, Prat A, Quintana FJ.Nature. 2020 Feb 12. doi: 10.1038/s41586-020-1999-0. [Epub ahead of print]
Multiple sclerosis is a chronic inflammatory disease of the CNS. Astrocytes contribute to the pathogenesis of multiple sclerosis, but little is known about the heterogeneity of astrocytes and its regulation. Here we report the analysis of astrocytes in multiple sclerosis and its preclinical model experimental autoimmune encephalomyelitis (EAE) by single-cell RNA and other sequencing. We identified astrocytes in EAE and multiple sclerosis that were characterized by decreased expression of NRF2 and increased expression of MAFG, which cooperates with MAT2α to represses antioxidant and anti-inflammatory transcriptional programs. Granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling in astrocytes drives the expression of MAFG and MAT2α and pro-inflammatory transcriptional modules, contributing to CNS pathology in EAE and, potentially, multiple sclerosis. Our results identify candidate therapeutic targets in multiple sclerosis.
This study went on a fishing trip to see what astrocytes were doing and pulled out a few targets.Will they be useful targets in MS? I don’t know but some of them are signalling molecules. I would say that I am not sure how good these are as targets. You not only have to get enough drug into brain then you have to get them in the cells and importantly these often lack specificity as they are found all over the place as is the case of MAFG. Recepors give the specificity the signalling molecules don’t. Why invent a new activation signalling pathway if you don’t need too. But hey what do I know? I got slagged off for picking some drug targets. But I say if you don’t know anything about the biology of the target and what it is doing, it is best to keep your mouth shut in case you look like a fool in the future. Therefore, I won’t say more until I interogate this information….More data to trawl.
Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that that regulates the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation. Dimethyl fumarate (and its metabolite, monomethyl fumarate) activates the NRF2 pathway. NFE2L2 has been shown to interact with MAFF, MAFG, MAFK, C-jun, CREBBP, EIF2AK3, KEAP1, and UBC. MafG gene expression is induced by oxidative stresses including .Mouse Mafg gene is induced by Nrf2-sMaf heterodimers through an antioxidant response element