ArticleAntioxidants & redox signaling2016
Repurposing the NRF2 Activator Dimethyl Fumarate as Therapy Against Synucleinopathy in Parkinson's Disease.
Article in Antioxidants & redox signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 2 of them syntheses that pooled it.
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Who cites it
170 citing papers in PubMed, 2 syntheses or guidelines pooled it, 267 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Pathophysiology and Therapeutic Perspectives of Oxidative Stress and Neurodegenerative Diseases: A Narrative Review.Advances in therapy · 2020Pooled it
- Review
- The irony of Parkinson's disease: Converging mechanisms of redox imbalance and ferroptosis.Redox biology · 2026Review
- Dual-Pathway Astrocyte Failure in Parkinson's Disease: Therapeutic Targeting of Nrf2/TFEB Suppression and cGAS-STING/Ferroptosis Activation.Molecular neurobiology · 2026Review
- The Glutamate-Glutathione axis in neuropsychiatric disorders and cancer: From shared mechanisms to non-invasive biomarkers.Redox biology · 2026Review
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Exercise and smoking: health rivals revealing shared protective mechanisms in Parkinson's?NPJ Parkinson's disease · 2026Review
- Microglial Nrf2 Activation Orchestrates Ferroptosis Inhibition and α-Synuclein Clearance in Parkinson's Disease.International journal of molecular sciences · 2026Article
- Hexaraphane as a potential therapeutic strategy for tauopathies.Redox biology · 2026Article
- Astrocytic dysfunction in Parkinson's disease pathogenesis: focusing on alpha-synuclein.Inflammopharmacology · 2026Review
- Neuroprotective role of bilirubin in Parkinson's disease.Frontiers in aging neuroscience · 2026Review
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- Beyond Antioxidants: The Emerging Role of Nrf2 Activation in Amyotrophic Lateral Sclerosis (ALS).International journal of molecular sciences · 2025Review
- Intersection of HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Integrative assessment of RNA sequencing and in silico analysis to pinpoint mRNAs, lncRNAs, and circRNAs interactions with miRNAs underlying arsenic-induced neurotoxicity.BMC genomics · 2025Article
- Regulatory Dynamics of Nrf2 With Sirtuins in the Brain: Exploring Cellular Metabolism, Synaptic Plasticity, and Defense Mechanisms.Journal of neurochemistry · 2025Review
- The role of NRF2 function and regulation in atherosclerosis: an update.Molecular and cellular biochemistry · 2025Review
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
110 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThis preclinical study was aimed at determining whether pharmacological targeting of transcription factor NRF2, a master controller of many homeostatic genes, might provide a disease-modifying therapy in the animal model of Parkinson's disease (PD) that best reproduces the main hallmark of this pathology, that is, α-synucleinopathy, and associated events, including nigral dopaminergic cell death, oxidative stress, and neuroinflammation.
resultsPharmacological activation of NRF2 was achieved at the basal ganglia by repurposing dimethyl fumarate (DMF), a drug already in use for the treatment of multiple sclerosis. Daily oral gavage of DMF protected nigral dopaminergic neurons against α-SYN toxicity and decreased astrocytosis and microgliosis after 1, 3, and 8 weeks from stereotaxic delivery to the ventral midbrain of recombinant adeno-associated viral vector expressing human α-synuclein. This protective effect was not observed in Nrf2-knockout mice. In vitro studies indicated that this neuroprotective effect was correlated with altered regulation of autophagy markers SQTSM1/p62 and LC3 in MN9D, BV2, and IMA 2.1 and with a shift in microglial dynamics toward a less pro-inflammatory and a more wound-healing phenotype. In postmortem samples of PD patients, the cytoprotective proteins associated with NRF2 expression, NQO1 and p62, were partly sequestered in Lewy bodies, suggesting impaired neuroprotective capacity of the NRF2 signature. INNOVATION: These experiments provide a compelling rationale for targeting NRF2 with DMF as a therapeutic strategy to reinforce endogenous brain defense mechanisms against PD-associated synucleinopathy.
conclusionDMF is ready for clinical validation in PD. Antioxid. Redox Signal. 25, 61-77.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.