Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 283, Issue -, Pages 74-85Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2015.04.006
Keywords
Dimethyl fumarate (DMF); Monomethyl fumarate (MMF); Monoethyl fumarate (MEF); Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B); Nuclear factor (elythroid-derived 2)-like 2 (Nrf2); Cytokine
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Funding
- Biogen
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Fumarate-containing pharmaceuticals are potent therapeutic agents that influence multiple cellular pathways. Despite proven clinical efficacy, there is a significant lack of data that directly defines the molecular mechanisms of action of related, yet distinct fumarate compounds. We systematically compared the impact of dimethyl fumarate (DMF), monomethyl fumarate (MMF) and a mixture of monoethyl fumarate salts (Ca++, Mg++, Zn++; MEF) on defined cellular responses. We demonstrate that DMF inhibited NF-kappa B-driven cytokine production and nuclear translocation of p65 and p52 in an Nrf2-independent manner. Equivalent doses of MMF and MEF did not affect NF-kappa B signaling. These results highlight a key difference in the biological impact of related, yet distinct fumarate compounds. (C) 2015 The Authors. Published by Elsevier B.V.
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