ArticleMolecular neurobiology2020
Activation of p62-Keap1-Nrf2 Pathway Protects 6-Hydroxydopamine-Induced Ferroptosis in Dopaminergic Cells.
Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 161 citations in OpenAlex.
- Modulation of the TGF-β/Smad Signaling Pathway by a Bioactive Oxidized Polygonati Rhizoma Polysaccharide Crosslinked Chitosan Hydrogel as Therapeutic Carrier for Parkinson's Disease Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nano-formulations in therapeutic strategies targeting cancer ferroptosis.Journal of pharmaceutical analysis · 2026Review
- Decode the Ubiquitinome in Parkinson's Disease: From Pathological Aggregates to Targeted DUB Therapeutics.Neuroscience bulletin · 2026Review
- Ferroptosis and aging: Inducing and catalyzing neurodegenerative diseases.Neural regeneration research · 2026Article
- When Pathways Converge: Iron, Lipid Peroxidation, and α-Synuclein in Ferroptosis-Driven Dopaminergic Neurodegeneration.Journal of neurochemistry · 2026Review
- Micro-nanoplastics and Parkinson's disease: evidence and perspectives.NPJ Parkinson's disease · 2026Review
- Identification of the mitochondria-related genePeerJ · 2026Article
- Targeting ferroptosis as a therapeutic strategy for hepatotoxicity.Toxicology reports · 2025Review
- Deciphering Ferroptosis-Related Astrocyte Subpopulations and Diagnostic Biomarkers in Parkinson's Disease through RNA Transcriptomics.Molecular neurobiology · 2025Article
- Nrf2-Keap1 Pathway and NLRP3 Inflammasome in Parkinson's Disease: Mechanistic Crosstalk and Therapeutic Implications.Molecular neurobiology · 2025Review
- Groundbreaking Insights Into SIRT1/NRF2-Mediated Ferroptosis Inhibition by Resveratrol in Parkinson's Disease Models.CNS neuroscience & therapeutics · 2025Article
- Co-treatment Strategy Supports Neuroprotection by Intersecting p62-Keap1-NRF2 and Autophagy Signaling Pathways in the Cellular Model of Parkinson's Disease.Cellular and molecular neurobiology · 2025Article
- HSPA4 restrains transferrin in dopaminergic neurons to attenuate ferroptosis in a Parkinson's disease model.Communications biology · 2025Article
- Epigenetic regulation of iron metabolism and ferroptosis in Parkinson's disease: Identifying novel epigenetic targets.Acta pharmacologica Sinica · 2025Review
- Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus.Molecular neurobiology · 2025Review
- Exploring the Updated Roles of Ferroptosis in Liver Diseases: Mechanisms, Regulators, and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- Induction of Ferroptotic Cell Death by Neuromelanin Pigments in Dopaminergic Cells.ACS chemical neuroscience · 2025Article
- EGCG Alleviates DSS-Induced Colitis by Inhibiting Ferroptosis Through the Activation of the Nrf2-GPX4 Pathway and Enhancing Iron Metabolism.Nutrients · 2025Article
- From pathogenesis to treatment: the emerging role of ferroptosis in Parkinson's disease.Frontiers in immunology · 2025Review
- Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.Current drug targets · 2025Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder primarily caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc). However, the manner of death of dopaminergic neurons remains indistinct. Ferroptosis is a form of cell death involving in the iron-dependent accumulation of glutathione depletion and lipid peroxide. Besides, previous studies indicated that ferroptosis might be involved in the death of dopaminergic neurons. In this study, we aim to explore the protective effect of the p62-Keap1-Nrf2 pathway against 6-hydroxydopamine (6-OHDA)-induced ferroptosis in dopaminergic cells. Firstly, our results demonstrated that 6-OHDA-induced ferroptosis could be observed in vivo zebrafish and in vitro human dopaminergic cell line (SH-SY5Y cells) model. Moreover, ferroptosis induced by 6-OHDA mitigates in SH-SY5Y cells upon ferrostatin-1 (Fer, an inhibitor of ferroptosis) treatment via upregulating the protein expression of glutathione peroxidase 4 (GPX4). Then, we found that high p62/SQSTM1 (p62) expression could protect SH-SY5Y cells against ferroptosis through promoting Nrf2 nuclear transfer and upregulating the expression of the antioxidant protein heme oxygenase-1 (HO-1). Ultimately, high p62 expression activates the Nrf2/HO-1 signaling pathway through binding to Kelch-like ECH-associated protein 1 (Keap1). Collectively, the activation of the p62-Keap1-Nrf2 pathway prevents 6-OHDA-induced ferroptosis in SH-SY5Y cells, targeting this pathway in combination with a pharmacological inhibitor of ferroptosis can be a potential approach for PD therapy.
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