ArticleAnnals of neurology2018
N-acetylcysteine targets 5 lipoxygenase-derived, toxic lipids and can synergize with prostaglandin E
Article in Annals of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 1 of them a synthesis that pooled it.
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Who cites it
178 citing papers in PubMed, 1 synthesis or guideline pooled it, 289 citations in OpenAlex.
- Ferroptosis in intracerebral hemorrhage: a bibliometric overview of mechanisms and future directions.Frontiers in cellular neuroscience · 2026Pooled it
- Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial.Frontiers in immunology · 2020Trial
- EGCG-loaded nanoparticles attenuate post-SAH white matter injury by targeting HO-1/S100A10 to suppress oxidative stress-induced reactive astrocytes.Redox report : communications in free radical research · 2026Article
- Bilirubin and the Yellow Players in Ferroptosis: A Delicate Balance in Human Health and Disease, with a Focus on the Liver, Cardiovascular System, and Brain.Biomolecules · 2026Review
- Cardiovascular Toxicity in Cancer Therapy: Potential Mechanisms of Ferroptosis and Treatment Strategies.Cells · 2026Review
- Microglial 5-LOX-activating protein antagonism alleviates leukotriene-driven neuroinflammation.Acta neuropathologica · 2026Article
- Arachidonic acid metabolism in spinal cord injury.Journal of advanced research · 2026Review
- Integrative gene target mapping, RNA sequencing, in silico molecular docking, ADMET profiling and molecular dynamics simulation study of marine derived molecules for type 1 diabetes mellitus.Molecular diversity · 2026Article
- N 6 -methyladenosine modification regulates cell death in cognitive impairment.Neural regeneration research · 2026Article
- Lipid Metabolism in Central Nervous System Diseases: Pathological Mechanisms and Therapeutic Advances.CNS neuroscience & therapeutics · 2026Review
- Microglial Mitochondrial Dysfunction: The Storm Center of Post-Stroke Neuroinflammation.CNS neuroscience & therapeutics · 2026Review
- Ferroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target.Molecular biomedicine · 2026Review
- The CaCell reports. Medicine · 2026Article
- Ironing out mechanisms of ferroptotic death to tailor new stroke therapies.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Pirin Transcriptionally Regulates PLA2G4A To Inhibit Ferroptosis in Colorectal Cancer via Lipid Profile Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Multilayered Landscape of Ferroptosis: Plasticity, Propagation, and Evolutionary Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Ferroptosis associated with secondary brain damage induced by hypertensive underlying biological processes in intracerebral hemorrhage and therapeutic prospects.European journal of medical research · 2026Review
- Acupuncture alleviates secondary brain injury in intracerebral hemorrhage-induced rats through activating the LKLF/Mfn2 pathway.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Article
- Insights into the potential pathogenesis and therapeutic implications of ferroptosis in brain microvascular endothelial cells during stroke.Frontiers in immunology · 2026Review
- Ferroptosis inhibitor UAMC-3203 preserves memory and prevents anxiety-like behavior but worsens aversive learning in diabetic rats after stroke in a randomized preclinical trial.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
118 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
20 authors at 12 institutions in 2 countries.
Funding
Abstract
objectivesN-acetylcysteine (NAC) is a clinically approved thiol-containing redox modulatory compound currently in trials for many neurological and psychiatric disorders. Although generically labeled as an "antioxidant," poor understanding of its site(s) of action is a barrier to its use in neurological practice. Here, we examined the efficacy and mechanism of action of NAC in rodent models of hemorrhagic stroke.
methodsHemin was used to model ferroptosis and hemorrhagic stroke in cultured neurons. Striatal infusion of collagenase was used to model intracerebral hemorrhage (ICH) in mice and rats. Chemical biology, targeted lipidomics, arachidonate 5-lipoxygenase (ALOX5) knockout mice, and viral-gene transfer were used to gain insight into the pharmacological targets and mechanism of action of NAC.
resultsNAC prevented hemin-induced ferroptosis by neutralizing toxic lipids generated by arachidonate-dependent ALOX5 activity. NAC efficacy required increases in glutathione and is correlated with suppression of reactive lipids by glutathione-dependent enzymes such as glutathione S-transferase. Accordingly, its protective effects were mimicked by chemical or molecular lipid peroxidation inhibitors. NAC delivered postinjury reduced neuronal death and improved functional recovery at least 7 days following ICH in mice and can synergize with clinically approved prostaglandin E
interpretationNAC is a promising, protective therapy for ICH, which acted to inhibit toxic arachidonic acid products of nuclear ALOX5 that synergized with exogenously delivered protective PGE
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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.