ArticleProceedings of the National Academy of Sciences of the United States of America2017
KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington's disease patients.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 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
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Role of lipoic acid in multiple sclerosis.CNS neuroscience & therapeutics · 2022Pooled it
- Translational Paradox of Triplet Repeat Expansion Disorders: Synthesizing Clinical Trial Failures to Guide Future Therapeutics.Clinical pharmacology and therapeutics · 2026Review
- Exercise-Driven NRF2 Activation as a Systemic Neuroprotective Strategy: Integrating Redox Biology, Muscle-Brain Crosstalk, and Therapeutic Targeting in Neurodegeneration.Biochemical genetics · 2026Review
- Ferroptosis in neurological diseases: moving towards therapeutic intervention.Molecular psychiatry · 2026Review
- Structural Characterization and Anti-Alzheimer's Disease Effect of Polysaccharides From Stellariae Radix.Food science & nutrition · 2026Article
- Programmed cell death pathways in huntington's disease: spotlight on ferroptosis and pyroptosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Coenzyme Q10 and Intracellular Signalling Pathways: Clinical Relevance.International journal of molecular sciences · 2025Review
- Intersection of HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Nrf2 signaling pathway: focus on oxidative stress in osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Review
- Genetically encoded biosensors of metabolic function for the study of neurodegeneration, a review and perspective.Neurophotonics · 2025Review
- Scutellarin Alleviates Bone Marrow Mesenchymal Stromal Cellular Senescence via the Ezh2-Nrf2 Signalling Axis in Diabetes-Induced Bone Loss.Cell proliferation · 2025Article
- Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury.Molecular neurobiology · 2025Review
- Emodin Improves Juvenile Largemouth Bass (Animals : an open access journal from MDPI · 2025Article
- In defence of ferroptosis.Signal transduction and targeted therapy · 2025Review
- Neural stem cells fate under neuroinflammatory conditions and oxidative stress response.Frontiers in cellular neuroscience · 2025Review
- Integrating Mitochondrial Biology into Innovative Cell Therapies for Neurodegenerative Diseases.Brain sciences · 2024Review
- Diabetic neuropathy: A NRF2 disease?Journal of diabetes · 2024Review
- Research on the anti-oxidant and anti-aging effects ofHeliyon · 2024Article
- The Role of NRF2 in Trinucleotide Repeat Expansion Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- Inhibiting the Keap1/Nrf2 Protein-Protein Interaction with Protein-Like Polymers.Advanced materials (Deerfield Beach, Fla.) · 2024Article
15 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
39 authors at 14 institutions in 6 countries.
Funding
Abstract
The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism by which this molecule activates NRF2 signaling. In a highly selective manner, the compound covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2. We further used this inducer to probe the functional consequences of selective activation of NRF2 signaling in Huntington's disease (HD) mouse and human model systems. Surprisingly, we discovered a muted NRF2 activation response in human HD neural stem cells, which was restored by genetic correction of the disease-causing mutation. In contrast, selective activation of NRF2 signaling potently repressed the release of the proinflammatory cytokine IL-6 in primary mouse HD and WT microglia and astrocytes. Moreover, in primary monocytes from HD patients and healthy subjects, NRF2 induction repressed expression of the proinflammatory cytokines IL-1, IL-6, IL-8, and TNFα. Together, our results demonstrate a multifaceted protective potential of NRF2 signaling in key cell types relevant to HD pathology.
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.