GSK-3β in myocardial ischemia-reperfusion injury: molecular insights and therapeutic approaches.

OBJECTIVES

To synthesize current evidence on the role of glycogen synthase kinase-3β (GSK-3β) in myocardial ischemia-reperfusion injury (MIRI) and evaluate its potential as a therapeutic target.

METHODS

This review examines the mechanistic involvement of GSK-3β in MIRI, focusing on mitochondrial permeability transition pore opening, apoptosis, inflammation, autophagy, and associated signaling pathways. Recent pharmacological advances in GSK-3β inhibition and their translational potential were also evaluated.

KEY FINDINGS: GSK-3β is a central regulator of the pathophysiological response to MIRI. Its temporal inactivation during reperfusion confers cardioprotection through pathways including PI3K/Akt and mTOR, whereas context-dependent activation may exacerbate myocardial injury. Recent GSK-3β inhibitors show therapeutic promise, although challenges including isoform selectivity and systemic toxicity remain.

CONCLUSIONS

GSK-3β represents a complex yet promising therapeutic target in ischemic heart disease. Future research should prioritize precision therapies and biomarker-guided interventions to improve the clinical translation of GSK-3β-targeted strategies.