ArticleJournal of pharmaceutical analysis2023
Celastrol targeting Nedd4 reduces Nrf2-mediated oxidative stress in astrocytes after ischemic stroke.
Article in Journal of pharmaceutical analysis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Sugiol Alleviates Cerebral Ischemia/Reperfusion Injury in the Early Phase Involving the LRRK2/NF-κB Pathway.Cell biochemistry and biophysics · 2026Article
- The Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Crosstalk Between Oxidative Stress and M1/M2 Microglial Polarization Following Ischemic Stroke.Molecular neurobiology · 2026Review
- Article
- Discovery of a novel Nrf2 activator that modulates mitochondrial function in neurons by regulating DHRS3-Nrf2 interaction after ischemic stroke.Theranostics · 2026Article
- Injectable Hyaluronic Acid-Functionalized Nanocomposite Hydrogel for Targeted Rheumatoid Arthritis Therapy via Concurrent ROS Attenuation and Macrophage Repolarization.International journal of nanomedicine · 2026Article
- Targeting the proteasome in cancer therapy: development and future opportunities in natural products.Frontiers in pharmacology · 2026Review
- AAD-2004 through clearing HScientific reports · 2025Article
- NEDD4 suppresses ferroptosis in lung ischemia-reperfusion injury by ubiquitinating and degrading SLC1A5.Scientific reports · 2025Article
- Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- Review
- Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects.Acta pharmaceutica Sinica. B · 2025Review
- An Integrated Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and Experimental Validation Study to Investigate the Potential Mechanism of Isoliquiritigenin in the Treatment of Ischemic Stroke.Current issues in molecular biology · 2025Article
- Emerging Target Discovery Strategies Drive the Decoding of Therapeutic Power of Natural Products and Further Drug Development: A Case Study of Celastrol.Exploration (Beijing, China) · 2025Review
- Role of autophagy in neurotoxic protein's clearance following post-ischemic stroke: where we are and what we know?Molecular brain · 2025Review
- The cryoprotective effects of celastrol nanoemulsion on post-thawed attributes and fertilizing ability of cryopreserved buffalo semen.Veterinary research communications · 2025Article
- The Role and Mechanisms of Ubiquitin-Proteasome System-Mediated Ferroptosis in Neurological Disorders.Neuroscience bulletin · 2025Review
- The role of celastrol in inflammation and diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- The role of astrocytes in ischemic stroke - mechanisms, functions and treatment.Frontiers in cell and developmental biology · 2025Review
- Antibodies Against Anti-Oxidant Enzymes in Autoimmune Glomerulonephritis and in Antibody-Mediated Graft Rejection.Antioxidants (Basel, Switzerland) · 2024Article
- Complex Inhibitory Activity of Pentacyclic Triterpenoids against Cutaneous Melanoma In Vitro and In Vivo: A Literature Review and Reconstruction of Their Melanoma-Related Protein Interactome.ACS pharmacology & translational science · 2024Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stroke is the second leading cause of death worldwide, and oxidative stress plays a crucial role. Celastrol exhibits strong antioxidant properties in several diseases; however, whether it can affect oxidation in cerebral ischemic-reperfusion injury (CIRI) remains unclear. This study aimed to determine whether celastrol could reduce oxidative damage during CIRI and to elucidate the underlying mechanisms. Here, we found that celastrol attenuated oxidative injury in CIRI by upregulating nuclear factor E2-related factor 2 (Nrf2). Using alkynyl-tagged celastrol and liquid chromatography-tandem mass spectrometry, we showed that celastrol directly bound to neuronally expressed developmentally downregulated 4 (Nedd4) and then released Nrf2 from Nedd4 in astrocytes. Nedd4 promoted the degradation of Nrf2 through K48-linked ubiquitination and thus contributed to astrocytic reactive oxygen species production in CIRI, which was significantly blocked by celastrol. Furthermore, by inhibiting oxidative stress and astrocyte activation, celastrol effectively rescued neurons from axon damage and apoptosis. Our study uncovered Nedd4 as a direct target of celastrol, and that celastrol exerts an antioxidative effect on astrocytes by inhibiting the interaction between Nedd4 and Nrf2 and reducing Nrf2 degradation in CIRI.
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