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Review
. 2023 Sep 7:14:1264842.
doi: 10.3389/fphar.2023.1264842. eCollection 2023.

Novel potential pharmacological applications of dimethyl fumarate-an overview and update

Giorgia Bresciani  1 , Federico Manai  2 , Sergio Davinelli  3 , Paolo Tucci  4 , Luciano Saso  5 , Marialaura Amadio  1
Affiliations
Review

Novel potential pharmacological applications of dimethyl fumarate-an overview and update

Giorgia Bresciani et al. Front Pharmacol. .

Abstract

Dimethyl fumarate (DMF) is an FDA-approved drug for the treatment of psoriasis and multiple sclerosis. DMF is known to stabilize the transcription factor Nrf2, which in turn induces the expression of antioxidant response element genes. It has also been shown that DMF influences autophagy and participates in the transcriptional control of inflammatory factors by inhibiting NF-κB and its downstream targets. DMF is receiving increasing attention for its potential to be repurposed for several diseases. This versatile molecule is indeed able to exert beneficial effects on different medical conditions through a pleiotropic mechanism, in virtue of its antioxidant, immunomodulatory, neuroprotective, anti-inflammatory, and anti-proliferative effects. A growing number of preclinical and clinical studies show that DMF may have important therapeutic implications for chronic diseases, such as cardiovascular and respiratory pathologies, cancer, eye disorders, neurodegenerative conditions, and systemic or organ specific inflammatory and immune-mediated diseases. This comprehensive review summarizes and highlights the plethora of DMF's beneficial effects and underlines its repurposing opportunities in a variety of clinical conditions.

Keywords: Nrf2 pathway; antioxidant; cardiovascular; dimethyl fumarate; drug repurposing; inflammation; neurodegenerative; oxidative stress.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
DMF’s immunomodulatory and antioxidative effects rely on its regulation of several pathways, among which the Keap1/Nrf2/ARE and NF-κB pathways, the modulation of GSH levels, its agonism of HCAR2 and its effects on the autophagic system. Based on these properties, DMF has sparked interest due to its potential repurposing for a variety of pathologies characterized or aggravated by inflammatory processes and oxidative stress. Abbreviations: dimethyl fumarate (DMF), glutathione (GSH), Hydroxycarboxylic Acid Receptor 2 (HCAR2), sequestrome 1 (p62/SQSTM1), Kelch-like ECH-associated protein (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), hemoxygenase-1 (HO1), quinoline oxidoreductase-1 (NQO1), superoxide dismutase (SOD).
FIGURE 2
FIGURE 2
Main pathological contexts reporting protective or beneficial effects of DMF treatment. Recent studies demonstrate DMF’s efficacy in several in vivo models of different pathologies; in particular, preclinical data is available on different cardiovascular, neurodegenerative, ocular and gastrointestinal diseases, as well as tumors, as shown in the picture. DMF’s effect is also being investigated in other pathologies outside of these main contexts (see text for additional information). Abbreviations: GBM: glioblastoma multiforme; CTCL: cutaneous T-cell lymphoma; NSCLC: non-small cells lung cancer; OSCC: oral squamous cell carcinoma; AML: acute myeloid leukemia.
See this image and copyright information in PMC

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