Insight into the mechanism of action of dimethyl fumarate in multiple sclerosis

J Mol Med (Berl). 2019 Apr;97(4):463-472. doi: 10.1007/s00109-019-01761-5. Epub 2019 Feb 28.

Abstract

Dimethyl fumarate (DMF) is an oral, disease-modifying agent for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, details regarding its mode of action are still emerging. It is believed that the mode of action of DMF involves both nuclear factor erythroid-derived 2-related factor (Nrf2)-dependent and independent pathways, which lead to an anti-inflammatory immune response due to type II myeloid cell and Th2 cell differentiation and neuroprotection. In this review, we will focus on the molecular and signaling effects of DMF that lead to changes in peripheral immune cell composition and function, alteration in CNS cell-specific functions, and effect on the blood-brain barrier.

Keywords: Dimethyl fumarate; Immunomodulation; Neuroprotection; Nuclear factor erythroid-derived 2-related factor; Relapsing–remitting multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dimethyl Fumarate / pharmacology
  • Dimethyl Fumarate / therapeutic use*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • NF-E2-Related Factor 2 / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology

Substances

  • Immunosuppressive Agents
  • NF-E2-Related Factor 2
  • Dimethyl Fumarate