Free radicals exert significant oxidative stress on tissues and cells and are implicated in the pathogenesis of neurodegenerative disorders such as multiple sclerosis (MS). The study by Scannevin et al. characterized the potential direct neuroprotective effects of dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) on cellular resistance to oxidative damage in primary cultures of central nervous system (CNS) cells and explored the dependence and function of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in this process. Using multiple assay formats, these studies indicate that both DMF and MMF are able to promote cytoprotective responses in cells by activating the Nrf2 pathway, enabling them to better withstand oxidative stress. The attenuation of H₂O₂-induced calcium accumulation, along with potential mitigation of other cellular events related to toxic oxidative challenge, resulted in MMF or DMF-dependent increase in viability in astrocytes and neurons in an Nrf2-dependent manner. The oxidative injury and challenge paradigms explored are highly relevant to the mechanistic damage that occurs in MS, and these preclinical studies using DMF and MMF collectively provide a compelling rationale for the use of DMF as a therapeutic agent in the treatment of MS.

See article at J Pharmacol Exp Ther 2012, 341:274–284.

• Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics