ArticleMedComm2025
Noncanonical feedback loop between "RIP3-MLKL" and "4EBP1-eIF4E" promotes neuronal necroptosis.
Article in MedComm, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Neuroprotective Mechanisms of Paeoniflorin in Parkinson's Models: Involvement of BDNF-Dependent PI3K/Akt and ERK/CREB Pathways.Current issues in molecular biology · 2026Article
- Thymosin Alpha-1 Provides Direct Neuroprotection by Engaging the Orexin Receptor HCRTR1 to Suppress Neuronal Necroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Artificial intelligence and peripheral neuropathies: Strategies for the development, application, and repair of regenerative biomaterials.Neural regeneration research · 2026Article
- Deciphering the rules of regulated cell death subroutines by in silico methods.Journal of advanced research · 2026Review
- Non-canonical role of "S6K1-SGK1" pathway in neuronal necroptosis following traumatic brain injury.Genes & diseases · 2026Article
- SFL-3D-cultured adipose mesenchymal cell-derived extracellular vesicles promote diabetic wound healing by alleviating microvascular endothelial senescenceBurns & trauma · 2026Article
- TAK1 activates PANoptosis through the NF-κB signalling pathway to delay diabetic wound healing.Burns & trauma · 2026Article
- [Geniposide inhibits retinal cell apoptosis induced by glaucoma through the Hspa1a pathway].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Si-Miao-Yong-An decoction suppresses necroptosis by regulating the p53 pathway in myocardial ischemia/reperfusion injury.Scientific reports · 2025Article
- DGKζ in Glycerophospholipid Metabolism Regulates the DAG and PA Balance and Interacts With PTEN to Alleviate Brain Damage in Septic Mice With Hydrogen Inhalation: A Comparative Metabolomic and Phosphoproteomic Analysis.Brain and behavior · 2025Article
- Periplocin induces necroptosis in papillary thyroid carcinoma through DR4 mediated RIPK3 and MLKL signaling.Scientific reports · 2025Article
- Solasodine suppresses nasopharyngeal carcinoma progression by inducing ferroptosis.Scientific reports · 2025Article
- Investigation of PANoptosis pathway in age-related macular degeneration triggered by Aβ1-40.Scientific reports · 2025Article
- Noncanonical feedback loop between "RIP3-MLKL" and "4EBP1-eIF4E" promotes neuronal necroptosis.MedComm · 2025Article
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stroke is a leading risk factor for disability and death. Necroptosis is involved in stroke pathogenesis. However, the molecular mechanisms underlying necroptosis in stroke remain unclear. The mammalian target of rapamycin complex 1 (mTORC1) modulates necroptosis in the gut epithelium. Eukaryotic translation initiation factor 4E (eIF4E)-binding protein-1 (4EPB1) is one of the main downstream molecules of mTORC1. This study addresses the role of the 4EBP1-eIF4E pathway in necroptosis. The 4EBP1-eIF4E pathway was found to be activated in both necroptotic HT-22 and mouse middle cerebral artery occlusion (MCAO) models. Functionally, 4EBP1 overexpression, eIF4E knockdown, and eIF4E inhibition suppressed necroptosis, respectively. Furthermore, a positive feedback circuit was observed between the 4EBP1-eIF4E and receptor-interacting protein-3 (RIP3)-mixed lineage kinase domain-like protein (MLKL) pathways, in which RIP3-MLKL activates the 4EBP1-eIF4E pathway by degrading 4EBP1 and activating eIF4E. This in turn enhanced RIP3-MLKL pathway activation. The eIF4E activation derived from this loop may stimulate cytokine production, which is a key factor associated with necroptosis. Finally, using a mouse MCAO model, the application of eIF4E, RIP3, and MLKL inhibitors was found to have a regulatory mechanism similar to that in the in vitro study, reducing the infarct volume and improving neurological function in MCAO mice.
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