ArticleCNS neuroscience & therapeutics2025
Knockdown of SESN2 Exacerbates Cerebral Ischemia-Reperfusion Injury Through Enhancing Glycolysis via the mTOR/HIF-1α Pathway.
Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Cell death in ischemia-reperfusion injury: beyond a single-cell-death perspective.Biomarker research · 2026Review
- Microglial Immunometabolic Remodeling After Ischemic Stroke: The Interplay Between Mitochondrial Stress and the Ischemic Microenvironment.Translational stroke research · 2026Review
- Glucose Transporter 1 in Health and Disease.MedComm · 2026Review
- Edaravone delivery of exosome-liposome hybrid nanoparticles for the treatment of ischemic stroke.Materials today. Bio · 2026Article
- Lactylation of PTBP1 drives a pro-apoptotic positive feedback loop in microglia following oxygen-glucose deprivation/reoxygenation-induced injury.Cell death & disease · 2026Article
- Review
- Investigating the Effect and Mechanism of Protocatechuic Aldehyde on Vascular Dementia Based on Multi-Omics Approach.Biomolecules · 2026Article
- Hexokinase 2 upregulation is associated with glycolytic reprogramming and neuroinflammation in hypoxic-ischemic brain damage: a therapeutic target for early intervention.Frontiers in immunology · 2026Article
- Comprehensive Bioinformatics Analysis and Experimental Verification RNF186 Is a Recurrence Signature Gene of Hepatocellular Carcinoma that Promotes Cell Proliferation.Oncology research · 2026Article
- Sestrin2 Knockdown Impairs Proliferation, Migration, Invasion, and Apoptosis in OSCC Cells via PI3K/AKT/mTOR and MAPK Pathways.Current issues in molecular biology · 2025Article
- VISTA Alleviates Microglia-Mediated Neuroinflammation After Cerebral Ischemia-Reperfusion Injury via Regulating ACOD1/Itaconic Acid Metabolism.Molecular neurobiology · 2025Article
- Developments in the study of the role of lactate metabolism in the genesis and progression of thyroid cancer.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
8 authors.
Funding
Abstract
aimReprogramming of glycometabolism plays a crucial role in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Sestrin2 (SESN2), a sensor upstream of the mTORC1, is closely related to glycometabolism. However, the effect and mechanism of SESN2 in CIRI are unclear. The goal of this research was to explore the effect of SESN2 on CIRI and its potential mechanisms related to glycometabolism.
methodsLentiviral vectors carrying SESN2 shRNA (Lenti-SESN2) or negative NC virus (Lenti-GFP) or rapamycin (mTOR inhibitor) were employed in the oxygen-glucose deprivation/reoxygenation (OGD/R) model and in the middle cerebral artery occlusion (MCAO) mice. In all, 3 days after I/R, neurological deficit scores and infarct size were assessed. The glycolysis and SESN2 levels were determined by RT-qPCR, Western blots, and immunofluorescence staining. Lactate levels were detected by a lactate assay kit, and the expression of the p-mTOR/HIF-1α signaling pathway was measured by immunofluorescence staining and protein blotting.
resultsLocal SESN2 deficiency in brain tissue increased the infarct size and reduced neurological scores 3 days after I/R. Moreover, the results showed that local SESN2 deficiency in brain tissue increased the expression of glycolysis-related proteins, including HK2, PFKM, PKM1, PKM2, and GLUT1. The lactate assay kit showed that local SESN2 deficiency in brain tissue increased lactate levels. In addition, local SESN2 deficiency in brain tissue improved the expression of the p-mTOR/HIF-1α pathway. However, rapamycin (RAP) treatment reversed these results, suggesting that SESN2 may influence IS injury by regulating glycometabolism via p-mTOR/HIF-1α pathway regulation. SESN2 knockdown in BV2 cells improved the glycolysis levels and the expression of the mTOR/HIF-1α pathway in the OGD/R model in vitro, but RAP treatment can also reverse these results.
conclusionsKnockdown of SESN2 in MCAO mice increased the expression of the p-mTOR/HIF-1α pathway, which increased glycolysis and lactate levels and, in turn, affected IS injury.
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