Mol Neurobiol. 2025 Nov 24;63(1):149. doi: 10.1007/s12035-025-05488-y.
ABSTRACT
Stroke is a vital cause of death worldwide. Ischemic stroke, a predominant type, is characterized by a sudden blockage of blood vessels supplying the brain, causing loss of blood flow. Restoring blood flow and oxygen in ischemic areas is the principal clinical treatment for ischemic stroke. Nevertheless, this process brings cerebral ischemia-reperfusion injury, which restrains the therapeutic effect on ischemic stroke. Plumbing the pathogenesis of brain injury and ischemia-reperfusion injury induced by ischemic stroke is crucial for improving stroke treatment. In this study, we analyzed differentially expressed genes in the penumbra of ischemic and ischemia-reperfusion rat brain tissue using transcriptome sequencing and screened out a gene PPP1R17 associated with mitophagy. We found that cerebral ischemia and ischemia-reperfusion induced PPP1R17 aggravated brain injury by repressing mitophagy. Mechanistically, PPP1R17 induces YAP1 phosphorylation by limiting the phosphatase activities of PP1 and PP2A and inhibits the activation of Pink1 and Parkin transcription by YAP1 as a transcriptional coregulator. In conclusion, PPP1R17 may serve as a potential therapeutic target for ameliorating cerebral ischemia and cerebral ischemia-reperfusion induced brain injury.
PMID:41276737 | DOI:10.1007/s12035-025-05488-y