The Role of Ferroptosis in Perioperative Neurocognitive Disorders

• Ferroptosis is a key pathological mechanism of PND. • Iron imbalance, neuroinflammation, ferroptosis form a linked cascade driving PND. • EGR1 bridges neuroinflammation and ferroptosis. • Targeting EGR1 shows potential for improving PND. Perioperative neurocognitive disorders (PND) have become a significant public health issue, given their negative impacts on postoperative recovery and the resultant increase in patients' financial burdens. The potential underlying mechanisms remain poorly understood. Currently, neuroinflammation is widely recognized as a core mechanism driving PND. Emerging evidence highlights its intimate association with brain iron homeostasis dysregulation, oxidative stress, and ferroptosis, all of which contribute to the pathogenesis of PND. In this review, we present a comprehensive overview of the mechanisms underlying ferroptosis and the intricate crosstalk among neuroinflammation, ferroptosis, and PND. Furthermore, we identify early growth response 1 (EGR1) as a potential target for inhibiting neuroinflammation, ferroptosis, and oxidative stress. Collectively, this review may provide novel insights into the role of ferroptosis in PND and inform new strategies for the clinical treatment of PND.