ArticleAntioxidants & redox signaling2013
Targeting Nrf2-mediated gene transcription by extremely potent synthetic triterpenoids attenuate dopaminergic neurotoxicity in the MPTP mouse model of Parkinson's disease.
Article in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.
- Genetic associations of Nrf2-encoding NFE2L2 variants with Parkinson's disease - a multicenter study.BMC medical genetics · 2014Pooled it
- Nrf2 activator peptide protects the brain from cerebral vascular dysfunction in alcohol ingestion.JCI insight · 2026Article
- Mechanistic Insights into the Metabolic Pathways and Neuroprotective Potential of Pentacyclic Triterpenoids: In-Depth Analysis of Betulin, Betulinic, and Ursolic Acids.Biomolecules · 2025Review
- Metabolomics profiling and neuroprotective effects of Lagerstroemia loudonii leaf extract and its kleptose CrysmebMetabolic brain disease · 2025Article
- Aqueous Extract ofInternational journal of molecular sciences · 2025Article
- Nrf2-Keap1 Pathway and NLRP3 Inflammasome in Parkinson's Disease: Mechanistic Crosstalk and Therapeutic Implications.Molecular neurobiology · 2025Review
- In vivo and in vitro perspectives in Parkinson's disease: Mechanisms and the role of phytomedicine.Journal of food and drug analysis · 2025Review
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Nitroxidative Stress, Cell-Signaling Pathways, and Manganese Porphyrins: Therapeutic Potential in Neuropathic Pain.International journal of molecular sciences · 2025Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson's Disease with Potential Therapeutic Implications.Biomolecules · 2025Review
- Development of LC-MS/MS method for cyanoenone triterpenoid determination to support CNS tissue distribution study.Bioanalysis · 2024Article
- A Complex Interplay of DJ-1, LRRK2, and Nrf2 in the Regulation of Mitochondrial Function in Cypermethrin-Induced Parkinsonism.Molecular neurobiology · 2024Article
- Neuroprotective effects of morroniside from Cornus officinalis sieb. Et zucc against Parkinson's disease via inhibiting oxidative stress and ferroptosis.BMC complementary medicine and therapies · 2023Article
- Mesenchymal stem-cell-derived microvesicles ameliorate MPTP-induced neurotoxicity in mice: a role of the gut-microbiota-brain axis.Psychopharmacology · 2023Article
- KEAP1-NRF2 protein-protein interaction inhibitors: Design, pharmacological properties and therapeutic potential.Medicinal research reviews · 2023Review
- The untapped potential of targeting NRF2 in neurodegenerative disease.Frontiers in aging · 2023Article
- Harnessing the Therapeutic Potential of the Nrf2/Bach1 Signaling Pathway in Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Article
- Neonatal 6-hydroxydopamine lesioning of rats and dopaminergic neurotoxicity: proposed animal model of Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
unlabelledAlthough the etiology of Parkinson's disease (PD) remains unclear, ample empirical evidence suggests that oxidative stress is a major player in the development of PD and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity. Nuclear factor E2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that upregulates a battery of antioxidant response element (ARE)-driven antioxidative and cytoprotective genes that defend against oxidative stress.
aimsWe evaluated whether the strategy of activation of Nrf2 and its downstream network of cytoprotective genes with small molecule synthetic triterpenoids (TP) attenuate MPTP-induced PD in mice.
resultsWe show that synthetic TP are thus far the most potent and direct activators of the Nrf2 pathway using a novel Neh2-luciferase reporter. They upregulate several cytoprotective genes, including those involved in glutathione biosynthesis in vitro. Oral administration of TP that were structurally modified to penetrate the brain-induced messenger RNA and protein levels for a battery of Nrf2-dependent cytoprotective genes reduced MPTP-induced oxidative stress and inflammation, and ameliorated dopaminergic neurotoxicity in mice. The neuroprotective effect of these TP against MPTP neurotoxicity was dependent on Nrf2, since treatment with TP in Nrf2 knockout mice failed to block against MPTP neurotoxicity and induce Nrf2-dependent cytoprotective genes. INNOVATION: Extremely potent synthetic TP that are direct activators of the Nrf2 pathway block dopaminergic neurodegeneration in the MPTP mouse model of PD.
conclusionOur results indicate that activation of Nrf2/antioxidant response element (ARE) signaling by synthetic TP is directly associated with their neuroprotective effects against MPTP neurotoxicity and suggest that targeting the Nrf2/ARE pathway is a promising approach for therapeutic intervention in PD.
Indexed as
Identifiers
What OpenQuestion holds
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.