ArticleRedox biology2022
TIGAR alleviates oxidative stress in brain with extended ischemia via a pentose phosphate pathway-independent manner.
Article in Redox biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Unveiling the "Glycolysis-Lactate-Lactylation" Axis: A Novel Target in Ischemic Cerebrovascular Disease.Neuroscience bulletin · 2026Review
- TIGAR overexpression alleviates intracerebral hemorrhage injury in mice by suppressing ATF4/NOX4/p22phox-mediated oxidative stress and inflammation.Acta pharmacologica Sinica · 2026Article
- Rethinking LPCAT3 roles in human disease: broadening perspectives beyond ferroptosis.Cell death & disease · 2026Review
- Molecularly self-assembled nanoplatforms for targeted ROS-scavenging and neuroinflammation alleviation in acute ischemic stroke.Materials today. Bio · 2026Article
- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- Comprehensive network pharmacology study on Huangjing Wan in the treatment of ischaemic stroke.Medicine · 2026Article
- TIGAR regulates intestinal mucus barrier integrity by inhibiting lactylation of G6PD/6PGD in ulcerative colitis.Nature communications · 2026Article
- TIGAR promotes osteogenic differentiation and ameliorates glucocorticoid-induced osteoporosis via autophagy-Nrf2-ROS axis.Genes & diseases · 2026Article
- TIGAR maintains intestinal epithelial regeneration by stabilizing HMGCL and promoting β-catenin β-hydroxybutyrylation in burn-induced sepsis.Cell death & disease · 2026Article
- Flipping the Switch: MeCP2-Mediated Lactylation Rewires Microglial Metabolism and Inflammation via the HK2/mTOR Axis in Poststroke Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Proteomic Analysis of Mouse Cerebral Cortex Following Experimental Ischemic Stroke: Identifying Novel Biomarkers of Damage and Repair.Cellular and molecular neurobiology · 2025Article
- Evaluation of the Degradation Effect of Zearalenone in feed by Bacillus amyloliquefaciens H6 and its Detoxification in Mice.Current microbiology · 2025Article
- TIGAR Suppresses ER Stress-Induced Neuronal Injury through Targeting ATF4 Signaling in Cerebral Ischemia/Reperfusion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Untargeted metabolomics unveils critical metabolic signatures in novel phenotypes of acute ischemic stroke.Metabolic brain disease · 2025Article
- Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson's Disease with Potential Therapeutic Implications.Biomolecules · 2025Review
- The impact of glycolysis on ischemic stroke: from molecular mechanisms to clinical applications.Frontiers in neurology · 2025Review
- In vivo Therapeutic Inhibition of the Tp53-Induced Glycolysis and Apoptosis Regulator (TIGAR) by Intravenous Administration of an Anti-Oncological siRNA-Biopolymer, TI6752 (Tituxistatin), in a Preclinical Xenograft Model of Colorectal Cancer.Journal of experimental pharmacology · 2025Article
- Isoliquiritigenin alleviates cerebral ischemia-reperfusion injury by reducing oxidative stress and ameliorating mitochondrial dysfunction via activating the Nrf2 pathway.Redox biology · 2024Article
- Dysfunction of astrocytic glycophagy exacerbates reperfusion injury in ischemic stroke.Redox biology · 2024Article
- Insulin attenuates LPS-induced cognitive impairment and ferroptosis through regulation of glucose metabolism in hippocampus.CNS neuroscience & therapeutics · 2024Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TP53-induced glycolysis and apoptosis regulator (TIGAR) alleviates oxidative stress and protects against ischemic neuronal injury by shifting glucose metabolism into the pentose phosphate pathway (PPP). However, the brain alters glucose metabolism from PPP to glycolysis during prolonged ischemia. It is still unknown whether and how TIGAR exerts the antioxidant activity and neuroprotection in prolonged ischemic brains. Here, we determined the significant upregulation of TIGAR that was proportional to the duration of ischemia. However, TIGAR failed to upregulate the NADPH level but still alleviated oxidative stress in neuronal cells with prolonged oxygen glucose-deprivation (OGD). Furthermore, inhibiting PPP activity, either by the expression of mutant TIGAR (which lacks enzymatic activity) or by silencing Glucose 6-phosphate dehydrogenase, still retained antioxidant effects and neuroprotection of TIGAR with prolonged OGD. Intriguingly, TIGAR-induced autophagy alleviated oxidative stress, contributing to neuron survival. Further experiments indicated that TIGAR-induced autophagy neutralized oxidative stress by activating Nrf2, which was cancelled by ML385 or Nrf2 knockdown. Remarkably, either Atg7 deletion or Nrf2 silencing abolished the neuroprotection of TIGAR in mice with prolonged ischemia. Taken together, we found a PPP-independent pathway in which TIGAR alleviates oxidative stress. TIGAR induces autophagy and, thus, activates Nrf2, offering sustainable antioxidant defense in brains with extended ischemia. This previously unexplored mechanism of TIGAR may serve as a critical compensation for antioxidant activity caused by the lack of glucose in 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.