ArticleCell death and differentiation2024
Itaconate protects ferroptotic neurons by alkylating GPx4 post stroke.
Article in Cell death and differentiation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Itaconate metabolism in regulated cell death.Molecular and cellular biochemistry · 2026Review
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Itaconic Acid Directly Binds to the Cysteine Residue of PurF: A Novel Mechanism for Inhibiting Purine Metabolism in Porcine PathogenicMicroorganisms · 2026Article
- Itaconate modifications: Mechanisms and applications.Journal of intensive medicine · 2026Review
- Betaine Inhibits Ferroptosis After Intracerebral Hemorrhage by Activating the Nrf2/HO-1 Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- Review
- Ferroptosis: unveiling a transformative perspective in the landscape of autoimmune diseases.Frontiers in immunology · 2026Review
- Metabolic control of neuroinflammation: focus on itaconate and its derivatives in CNS disorders.Frontiers in immunology · 2026Review
- Dimethyl itaconate suppresses dendritic cell and CD8BMC medicine · 2025Article
- Lung protective ventilation alleviates intracerebral hemorrhage-induced secondary brain and lung injury in mice via the Nrf2/HO‑1 pathway.Journal of thoracic disease · 2025Article
- 4-octyl Itaconate Attenuates Acute Pancreatitis and Associated Lung Injury by Suppressing Ferroptosis in Mice.Inflammation · 2025Article
- Acod1 Promotes PAD4 Ubiquitination via UBR5 Alkylation to Modulate NETosis and Exert Protective Effects in Sepsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Organic AIE Nanoradiosensitizer Potentiates X-Ray Triggered Continuous Reactive Oxygen Species Generation for Potent Cancer Radioimmunotherapy.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- H3K14 lactylation exacerbates neuronal ferroptosis by inhibiting calcium efflux following intracerebral hemorrhagic stroke.Cell death & disease · 2025Article
- Single-cell and Spatial Transcriptomics Reveals Ferroptosis as The Most Enriched Programmed Cell Death Process in Hemorrhage Stroke-induced Oligodendrocyte-mediated White Matter Injury.International journal of biological sciences · 2024Article
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
Neuronal ferroptosis plays a key role in neurologic deficits post intracerebral hemorrhage (ICH). However, the endogenous regulation of rescuing ferroptotic neurons is largely unexplored. Here, we analyzed the integrated alteration of metabolomic landscape after ICH using LC-MS and MALDI-TOF/TOF MS, and demonstrated that aconitate decarboxylase 1 (Irg1) and its product itaconate, a derivative of the tricarboxylic acid cycle, were protectively upregulated. Deficiency of Irg1 or depletion of neuronal Irg1 in striatal neurons was shown to exaggerate neuronal loss and behavioral dysfunction in an ICH mouse model using transgenic mice. Administration of 4-Octyl itaconate (4-OI), a cell-permeable itaconate derivative, and neuronal Irg1 overexpression protected neurons in vivo. In addition, itaconate inhibited ferroptosis in cortical neurons derived from mouse and human induced pluripotent stem cells in vitro. Mechanistically, we demonstrated that itaconate alkylated glutathione peroxidase 4 (GPx4) on its cysteine 66 and the modification allosterically enhanced GPx4's enzymatic activity by using a bioorthogonal probe, itaconate-alkyne (ITalk), and a GPx4 activity assay using phosphatidylcholine hydroperoxide. Altogether, our research suggested that Irg1/itaconate-GPx4 axis may be a future therapeutic strategy for protecting neurons from ferroptosis post ICH.
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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.