Targeting Drp1 in Cerebral Ischemia-Reperfusion Injury: Mechanisms and Therapeutic Implications.

BACKGROUND

Cerebral ischemia-reperfusion injury (CIRI) arises after blood flow restoration in stroke, where reperfusion paradoxically triggers mitochondrial dysfunction, apoptosis, inflammation, and oxidative stress. Dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, amplifies these cascades by promoting apoptosis, inflammatory signaling, and calcium imbalance.

METHODS

This review synthesizes recent studies on Drp1 in CIRI, focusing on its regulatory roles in mitochondrial dynamics and neuronal injury, and evaluating therapeutic strategies through pharmacological and genetic modulation.

RESULTS

Evidence shows Drp1 inhibition mitigates CIRI in preclinical models by restoring mitochondrial homeostasis, reducing oxidative stress, and improving neuronal survival. Promising interventions include selective inhibitors and genetic approaches, though challenges remain regarding drug specificity, delivery efficiency, and long-term safety.

CONCLUSION

Drp1 is central to CIRI pathology and represents a promising therapeutic target. Future work should prioritize advanced delivery systems and safer, more selective Drp1 modulators to enable clinical translation.