ArticlePLoS genetics2017
Direct Keap1-Nrf2 disruption as a potential therapeutic target for Alzheimer's disease.
Article in PLoS genetics, 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, 141 citations in OpenAlex.
- Therapeutic Targeting of Proteostasis in Amyotrophic Lateral Sclerosis-a Systematic Review and Meta-Analysis of Preclinical Research.Frontiers in neuroscience · 2020Pooled it
- The emerging role of circular RNAs in neurodegenerative diseases and viral infections.Journal of neurovirology · 2026Review
- Dimercaprol Reprograms Intestinal Redox Homeostasis and Organelle Crosstalk to Combat Iron-Induced Gut Dysbiosis Through NRF2/HO-1 Signaling.Antioxidants (Basel, Switzerland) · 2026Article
- Discovery of a novel Keap1 inhibitor for neurodegeneration through virtual screening and molecular dynamics simulations.PloS one · 2026Article
- A study to determine the effect of nano-selenium and thymoquinone on the Nrf2 gene expression in Alzheimer's disease.Future science OA · 2025Article
- Beyond the Genotype: A Multi-Omic Analysis of APOEe4's Role in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2025Article
- Sensing within: Mitochondrial inside-out signal transduction.Cell chemical biology · 2025Review
- Perspectives on Alzheimer's Disease Treatment Based on Counteracting Oxidative Stress.Biomolecules · 2025Review
- Alzheimer's Disease Pathogenic Mechanisms: Linking Redox Homeostasis and Mitochondria-Associated Metabolic Pathways Through Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2).Antioxidants (Basel, Switzerland) · 2025Review
- Enhancing autophagy by redox regulation extends lifespan in Drosophila.Nature communications · 2025Article
- Nutraceutical Strategies for Targeting Mitochondrial Dysfunction in Neurodegenerative Diseases.Foods (Basel, Switzerland) · 2025Review
- Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations.Molecular neurobiology · 2025Review
- Natural Products in the Treatment of Neuroinflammation at Microglia: Recent Trend and Features.Cells · 2025Review
- Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury.Molecular neurobiology · 2025Review
- Mechanistic Insights and Potential Therapeutic Implications of NRF2 in Diabetic Encephalopathy.Molecular neurobiology · 2024Review
- Activation of the Keap1/Nrf2 pathway suppresses mitochondrial dysfunction, oxidative stress, and motor phenotypes inLife science alliance · 2024Article
- Research on the Anti-Fatigue Effects and Mechanisms of Arecoline in Sleep-Deprived Mice.Nutrients · 2024Article
- New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview.Pharmacological reviews · 2024Review
- Inhibiting the Keap1/Nrf2 Protein-Protein Interaction with Protein-Like Polymers.Advanced materials (Deerfield Beach, Fla.) · 2024Article
- Dioxinodehydroeckol: A Potential Neuroprotective Marine Compound Identified by In Silico Screening for the Treatment and Management of Multiple Brain Disorders.Molecular biotechnology · 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
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Nrf2, a transcriptional activator of cell protection genes, is an attractive therapeutic target for the prevention of neurodegenerative diseases, including Alzheimer's disease (AD). Current Nrf2 activators, however, may exert toxicity and pathway over-activation can induce detrimental effects. An understanding of the mechanisms mediating Nrf2 inhibition in neurodegenerative conditions may therefore direct the design of drugs targeted for the prevention of these diseases with minimal side-effects. Our study provides the first in vivo evidence that specific inhibition of Keap1, a negative regulator of Nrf2, can prevent neuronal toxicity in response to the AD-initiating Aβ42 peptide, in correlation with Nrf2 activation. Comparatively, lithium, an inhibitor of the Nrf2 suppressor GSK-3, prevented Aβ42 toxicity by mechanisms independent of Nrf2. A new direct inhibitor of the Keap1-Nrf2 binding domain also prevented synaptotoxicity mediated by naturally-derived Aβ oligomers in mouse cortical neurons. Overall, our findings highlight Keap1 specifically as an efficient target for the re-activation of Nrf2 in AD, and support the further investigation of direct Keap1 inhibitors for the prevention of neurodegeneration in vivo.
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.