ReviewAntioxidants (Basel, Switzerland)2024
Nrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases.
Review in Antioxidants (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Trace Elements Dyshomeostasis and Toxic Metals Neurotoxicity in Neurodegenerative Diseases.Biological trace element research · 2026Review
- The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.Molecular and cellular biochemistry · 2026Review
- Synergistic Effects of Selenium, Selenoproteins, Selenocysteine and Procyanidin A2 Based on Immune Response and Oxidative Stress.Molecules (Basel, Switzerland) · 2026Review
- Nrf2 Activators in Parkinson's Disease: Modulating Mitophagy and Regulating Cuproptosis.Molecular neurobiology · 2026Review
- Targeting Neuroinflammation and Oxidative Stress to Slow Neurodegeneration in the Visual System.Journal of clinical medicine · 2026Review
- Ferroptosis and Nrf-2 signaling: a redox tug of war in leishmaniasis pathogenesis and host directed therapy.Redox biology · 2026Review
- Neuroinflammation: a critical bridge linking peripheral pathology and age-related degeneration in myasthenia gravis.Frontiers in medicine · 2026Review
- Fumarate and fumarate hydratase: an immunometabolite regulator of inflammation and diseases.Frontiers in immunology · 2026Review
- Dimethyl fumarate therapy in a Western diet pregnancy model: a pilot study in guinea pigs.PeerJ · 2026Article
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- Phagocyte NADPH Oxidase NOX2-Derived Reactive Oxygen Species in Antimicrobial Defense: Mechanisms, Regulation, and Therapeutic Potential-A Narrative Review.Antioxidants (Basel, Switzerland) · 2025Review
- Da-Bu-Yin-Wan and Qian-Zheng-San Alleviate Parkinson's Disease by Activating the Keap1/Nrf2/HO-1 Pathway to Positively Regulate Oxidative Stress.CNS neuroscience & therapeutics · 2025Article
- Dimethyl Fumarate vs. Monomethyl Fumarate: Unresolved Pharmacologic Issues.Pharmaceutics · 2025Review
- Repurposing dimethyl fumarate for cancer therapy: current evidence and future directions.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is a potential therapeutic target for central nervous system diseases. This review emphasizes the role of oxidative stress and neuroinflammation in neurodegenerative diseases, highlighting the therapeutic potential of Nrf2 activators such as dimethyl fumarate (DMF). DMF, initially administered for treating psoriasis, has demonstrated efficacy in multiple sclerosis and is metabolized to monomethyl fumarate, which may exert significant therapeutic effects. DMF activates the Nrf2-ARE pathway, and recent studies have indicated that its anti-inflammatory effects occur through Nrf2-independent mechanisms. Electrophilic Nrf2 activators, such as DMF, covalently bind to cysteine residues in proteins and modulate their function. We discuss the implications of cysteine residue modifications by DMF, which may cause both therapeutic benefits and potential off-target effects. Furthermore, we propose a chemical proteomics-based drug discovery approach to achieve desired therapeutic effects by selectively covalently modifying cysteines in target proteins. These findings advocate for a broader understanding of the Nrf2-independent mechanisms of electrophilic Nrf2 activators, thereby improving drug discovery strategies that target neurodegenerative diseases while minimizing toxicity.
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Registered trials
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