ArticleAntioxidants (Basel, Switzerland)2022
Oxidative Stress-Induced Misfolding and Inclusion Formation of Nrf2 and Keap1.
Article in Antioxidants (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Oxidative Stress in Animals: A Systematic Analysis from Signaling Pathways to Biological Effects.Life (Basel, Switzerland) · 2026Review
- Article
- Beyond the structure-function paradigm: A comprehensive review of intrinsically disordered proteins.Biochemistry and biophysics reports · 2026Review
- Glutathione Biology in Neurodegenerative and Metabolic Diseases: Molecular Mechanisms, Pathophysiological Roles, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Oxygen Exposure in Patients with Brain Injury: Beyond Static Thresholds.Neurocritical care · 2026Article
- Nootkatone confers MAOB-dependent neuroprotection against ferroptotic injury via brain-targeted nanoparticle delivery in ischemic stroke.Journal of nanobiotechnology · 2026Article
- Design, Synthesis, and Biological Evaluation of Novel Vinyl Selenone Derivatives as Potent Nrf2 Activators for Atopic Dermatitis.Journal of medicinal chemistry · 2026Article
- γ-Glutamylcysteine Alleviates t-BHP-Induced Oxidative Damage in NIH/3T3 Fibroblasts by Promoting Nuclear Translocation of Nrf2.Food science & nutrition · 2026Article
- Nrf2 Modulation by Natural Compounds in Aging, Neurodegeneration, and Neuropathic Pain.Pharmaceutics · 2026Review
- Oxymatrine alleviates symptoms in high-fat diet and STZ-induced SD rats with painful diabetic neuropathy by reducing inflammation and oxidative stress.Frontiers in immunology · 2026Article
- Oxidative Stress-Driven Cellular Senescence: Mechanistic Crosstalk and Therapeutic Horizons.Antioxidants (Basel, Switzerland) · 2025Review
- The protective effect of naringenin on ulcerative colitis in mice through increasing Nrf2 pathway activity.Acta biochimica et biophysica Sinica · 2025Article
- Lipid Oxidation at the Crossroads: Oxidative Stress and Neurodegeneration Explored inAntioxidants (Basel, Switzerland) · 2025Review
- Rosmarinic Acid AmelioratesInternational journal of molecular sciences · 2024Article
- New insights into crosstalk between Nrf2 pathway and ferroptosis in lung disease.Cell death & disease · 2024Review
- The role and mechanism of cinnamaldehyde in cancer.Journal of food and drug analysis · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cells that experience high levels of oxidative stress respond by inducing antioxidant proteins through activation of the protein transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 is negatively regulated by the E3 ubiquitin ligase Kelch-like ECH-associated protein 1 (Keap1), which binds to Nrf2 to facilitate its ubiquitination and ensuing proteasomal degradation under basal conditions. Here, we studied protein folding and misfolding in Nrf2 and Keap1 in yeast, mammalian cells, and purified proteins under oxidative stress conditions. Both Nrf2 and Keap1 are susceptible to protein misfolding and inclusion formation upon oxidative stress. We propose that the intrinsically disordered regions within Nrf2 and the high cysteine content of Keap1 contribute to their oxidation and the ensuing misfolding. Our work reveals previously unexplored aspects of Nrf2 and Keap1 regulation and/or dysregulation by oxidation-induced protein misfolding.
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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.