Noncanonical feedback loop between "RIP3-MLKL" and "4EBP1-eIF4E" promotes neuronal necroptosis.

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

SUBMITTER: Wang S 

PROVIDER: S-EPMC11836343 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature