title: [Neuronal dysfunction in multiple sclerosis].
abstract: The precise mechanisms of cortical damage in multiple sclerosis (MS) remain unknown. Microglia, the resident immune cells in the central nervous system (CNS), are involved in the chronic neuroinflammation in MS cortical lesions. Microglia produce various inflammatory cytokines such as IFN-γ and IL-β, reactive oxygen species, and glutamate. IL-β secretion is induced by NLRP3. ROS is induced by GM-CSF-producing Th17 cells. Glutamate is released via gap junctions. These molecules exert neurotoxicity. Meanwhile, damaged neurons produce fractalkine and FGF-2, which suppress microglial activation and enhance microglial neuroprotection through anti-inflammatory and anti-oxidant effect. Fractalkine accelerates microglial clearance of neuronal debris via inducing the release of MFG-E8. FGF-2 induces microglial migration through the FGFR3-Wnt-ERK signaling pathway. These molecules suppress microglial neuroinflammation, and enhance neuroprotection, which may give us clues for future therapeutic strategy cortical damage in MS.
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
mesh_terms: D000893:Anti-Inflammatory Agents; D000954:Antigens, Surface / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D002540:Cerebral Cortex / Q000473:pathology*; D054428:Chemokine CX3CL1 / Q000378:metabolism / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D017629:Gap Junctions / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000633:toxicity; D053583:Interleukin-1beta / Q000378:metabolism / Q000633:toxicity; D020935:MAP Kinase Signaling System; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008894:Milk Proteins / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009103:Multiple Sclerosis / Q000235:genetics / Q000473:pathology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000502:physiology; D058504:Th17 Cells / Q000502:physiology; D060449:Wnt Signaling Pathway
chemical_list: D000893:Anti-Inflammatory Agents; D000954:Antigens, Surface; D000975:Antioxidants; D002352:Carrier Proteins; D054428:Chemokine CX3CL1; D005971:Glutamates; D053583:Interleukin-1beta; C098942:MFGE8 protein, human; D008894:Milk Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016222:Fibroblast Growth Factor 2; D007371:Interferon-gamma; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3