ArticleCell death & disease2023
Crocetin antagonizes parthanatos in ischemic stroke via inhibiting NOX2 and preserving mitochondrial hexokinase-I.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- PDK4-Associated Metabolic Reprogramming Contributes to Lactate Accumulation and Parthanatos-Related Changes in Septic Cardiomyocytes.Cardiovascular drugs and therapy · 2026Article
- Research Progress on Novel Lead Compounds for Central Nervous System Diseases.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeting DNA Damage and Repair Pathways in Cerebral Ischemic Stroke: From Bench to Bedside.Translational stroke research · 2026Review
- Ferroptosis and Its Crosstalk with Other Cell Death Modes in Ischemic Stroke.Current medicinal chemistry · 2026Review
- Neuroprotective potential of indian herbs in ischaemic stroke: a comprehensive review of pharmacological insights, therapeutic gaps, and future directions.Inflammopharmacology · 2025Review
- Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025Review
- METTL3-dependent mAutophagy · 2025Article
- PARylation promotes acute kidney injuryActa pharmaceutica Sinica. B · 2025Article
- Role of mitochondrial metabolism in ischemic stroke and natural products intervention.Molecular biology reports · 2025Review
- Safflower Yellow Pigment Alleviates Cerebral Ischemia-Reperfusion Injury via Protein Nitration and Oxidative Modulation.Brain and behavior · 2025Article
- Environmental enrichment: a neurostimulatory approach to aging and ischemic stroke recovery and rehabilitation.Biogerontology · 2025Review
- Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting the PARylation-Dependent Ubiquitination Signaling Pathway for Cancer Therapies.Biomolecules · 2025Review
- DNA2 knockout aggravates cerebral ischemia/reperfusion injury by reducing postsynaptic Homer1a.Zoological research · 2025Article
- Advances in non-apoptotic regulated cell death: implications for malignant tumor treatment.Frontiers in oncology · 2025Review
- Advancements in nasal drug delivery system of natural products.Frontiers in pharmacology · 2025Review
- Parthanatos and apoptosis: unraveling their roles in cancer cell death and therapy resistance.EXCLI journal · 2025Review
- Ozone therapy mitigates parthanatos after ischemic stroke.Biological research · 2024Article
- Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke.Biochemical pharmacology · 2024Review
- The Influence of Oxidative Stress Markers in Patients with Ischemic Stroke.Biomolecules · 2024Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parthanatos is one of the major pathways of programmed cell death in ischemic stroke characterized by DNA damage, poly (ADP-ribose) polymerases (PARP) activation, and poly (ADP-ribose) (PAR) formation. Here we demonstrate that crocetin, a natural potent antioxidant compound from Crocus sativus, antagonizes parthanatos in ischemic stroke. We reveal that mechanistically, crocetin inhibits NADPH oxidase 2 (NOX2) activation to reduce reactive oxygen species (ROS) and PAR production at the early stage of parthanatos. Meanwhile we demonstrate that PARylated hexokinase-I (HK-I) is a novel substrate of E3 ligase RNF146 and that crocetin interacts with HK-I to suppress RNF146-mediated HK-I degradation at the later stage of parthanatos, preventing mitochondrial dysfunction and DNA damage that ultimately trigger the irreversible cell death. Our study supports further development of crocetin as a potential drug candidate for preventing and/or treating ischemic stroke.
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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.