ArticleSignal transduction and targeted therapy2022
Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers, 2 of them syntheses 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
177 citing papers in PubMed, 2 syntheses or guidelines pooled it, 295 citations in OpenAlex.
- Modulation of miRNAs by Phytochemicals in Cerebral Ischemia: A Systematic Review of In Vitro and In Vivo Studies.Phytotherapy research : PTR · 2025Pooled it
- Experimental Evidence on Acupuncture Targeting Ferroptosis for Neurological Function Improvement in Cerebral Stroke: A Systematic Review and Meta-Analysis.Brain and behavior · 2025Pooled it
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Deciphering the rules of regulated cell death subroutines by in silico methods.Journal of advanced research · 2026Review
- Shh-S100A10 axis curbs neuronal PANoptosis after ischemic stroke.Neural regeneration research · 2026Article
- Lineage-specific Nrf2 signaling orchestrates distinct neuroprotective mechanisms in acute ischemic stroke.Cell death & disease · 2026Article
- Electroacupuncture Attenuates Cerebral Ischemia-Reperfusion Injury via Vagus Nerve-α7 Nicotinic Acetylcholine Receptor-Dependent Microglial Polarization.Journal of the American Heart Association · 2026Article
- ACSL4 in Alzheimer's disease: Pathogenetic mechanisms and potential therapeutic targets.Genes & diseases · 2026Review
- Huashi Baidu formula may attenuate adriamycin-induced myocardial injury via modulating NRF2-ATF3-SRXN1 axis-mediated ferroptosis.Chinese herbal medicines · 2026Article
- Review
- Isoleucyl-tRNA synthetase 1 mutation impairs pulmonary surfactant homeostasis by disrupting alveolar macrophage function.Respiratory research · 2026Article
- DLL1-mediated ferroptosis resistance via the Notch-Nrf2/GPX4 axis drives cisplatin resistance in ovarian cancer.Cancer & metabolism · 2026Article
- Metabolic Adaptation in Acute Ischemic Events: The Critical Role of Acyl-Coenzyme A Synthetase Family in Myocardial Infarction and Ischemic Stroke.Journal of the American Heart Association · 2026Review
- Androgen receptors protect against thoracic aortic dissection via inhibiting ferroptosis of vascular smooth muscle cells in male patients.Chinese medical journal · 2026Article
- Atypical involvement of Alzheimer's tau proteins in diseases beyond tauopathies.Life medicine · 2026Review
- Toosendanin Alleviates Cerebral Ischemia/Reperfusion Injury via Inhibiting Neural Ferroptosis Through Lipid Metabolic Reprogramming in MCAO Mice.CNS neuroscience & therapeutics · 2026Article
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Ferroptosis in neurological diseases: moving towards therapeutic intervention.Molecular psychiatry · 2026Review
- Roles of ACSL6 in lipid homeostasis and stress responses in the nervous system.Metabolic brain disease · 2026Review
- Interference with HMGB1 Inhibits Neuronal Ferroptosis Following Spinal Cord Injury through Targeting ACSL4.Neurochemical research · 2026Article
117 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
24 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ischemic stroke represents a significant danger to human beings, especially the elderly. Interventions are only available to remove the clot, and the mechanism of neuronal death during ischemic stroke is still in debate. Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs. Here we report that the serine protease, thrombin, instigates ferroptotic signaling by promoting arachidonic acid mobilization and subsequent esterification by the ferroptotic gene, acyl-CoA synthetase long-chain family member 4 (ACSL4). An unbiased multi-omics approach identified thrombin and ACSL4 genes/proteins, and their pro-ferroptotic phosphatidylethanolamine lipid products, as prominently altered upon the middle cerebral artery occlusion in rodents. Genetically or pharmacologically inhibiting multiple points in this pathway attenuated outcomes of models of ischemia in vitro and in vivo. Therefore, the thrombin-ACSL4 axis may be a key therapeutic target to ameliorate ferroptotic neuronal injury during ischemic stroke.
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.