期刊
JOURNAL OF NEUROIMMUNOLOGY
卷 299, 期 -, 页码 35-44出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2016.08.006
关键词
Dimethyl fumarate; Monomethyl fumarate; Microglia; LPS plus IFN-gamma; Mitochondrial respiration; Cytokine
资金
- Biogen, Inc.
Delayed-release dimethyl fumarate (DMF) is an approved treatment for multiple sclerosis (MS). Microglia are considered central to MS pathophysiology, however the effects of DMF and the primary metabolite monomethyl fumarate (MMF) on microglia are not well characterized. We demonstrated that DMF and MMF altered transcriptional responses in primary microglia related to the nuclear factor (erythroid-derived 2)-like 2 pathway. Additionally, through an NRF2 independent manner, DMF, but not MMF significantly reduced production of proinflammatory mediators in classically activated microglia, and further rescued mitochondrial respiratory deficits in primary cortical neurons that were induced by activated microglia. These data suggest the mechanism of action of DMF may involve modulation of microglia inflammatory responses and attenuation of neurotoxicity. (C) 2016 Elsevier B.V. All rights reserved.
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