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Updated: Mar 13, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Dimethyl fumarate alters microglia phenotype and protects neurons against proinflammatory toxic microenvironments
Haiyan Peng1, Huo Li1, Adam Sheehy1
1Biogen, Inc., 225 Binney St, Cambridge, MA 02142, United States.
Abstract:
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.
Insights
Dimethyl fumarate (DMF) modulates microglia, reducing inflammation and neurotoxicity in multiple sclerosis (MS) models. This suggests DMF
Area of Science:
- Neuroimmunology
- Pharmacology
Background:
- Microglia play a key role in multiple sclerosis (MS) pathophysiology.
- The precise effects of dimethyl fumarate (DMF) and its metabolite monomethyl fumarate (MMF) on microglia remain incompletely understood.
Purpose of the Study:
- To investigate the impact of DMF and MMF on microglial activation and function.
- To elucidate the molecular mechanisms underlying DMF's therapeutic effects in MS.
Main Methods:
- Primary microglia were treated with DMF and MMF.
- Transcriptional responses were analyzed, focusing on the nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway.
- Proinflammatory mediator production and neuronal mitochondrial function were assessed.
Main Results:
- Both DMF and MMF altered transcriptional profiles in microglia, involving the NRF2 pathway.
- DMF, independently of NRF2, suppressed proinflammatory mediator release from classically activated microglia.
- DMF mitigated microglial-induced mitochondrial dysfunction in primary cortical neurons.
Conclusions:
- DMF's mechanism of action in MS may involve the modulation of microglial inflammatory responses.
- DMF demonstrates neuroprotective effects by attenuating microglial-induced neurotoxicity.
