The potential role of GSTO1 in perioperative neurocognitive disorders: a mechanistic hypothesis

Perioperative neurocognitive disorders (PND) are common and devastating perioperative neurological complications that markedly hinder postoperative rehabilitation and impair long-term quality of life in elderly surgical patients. Oxidative stress and neuroinflammation are well-established core pathogenic drivers of PND, whereas the key molecular mediators bridging perioperative stress and cognitive dysfunction remain poorly elucidated. Glutathione S-transferase Omega 1 (GSTO1) is a multifunctional deglutathionylase that centrally governs intracellular redox homeostasis and inflammatory signal transduction. Notably, no direct clinical or preclinical perioperative evidence has validated the modulatory effects of surgical trauma or anesthetic exposure on GSTO1 expression and catalytic activity, identifying GSTO1 as a promising yet unverified molecular linker between perioperative oxidative/inflammatory insults and PND progression. Accumulating indirect mechanistic evidence from chronic neurodegenerative disease models confirms the essential regulatory function of GSTO1 in conserved oxidative and inflammatory cascades shared by chronic cognitive degeneration and acute perioperative brain injury. This narrative review systematically elaborates the structural characteristics, enzymatic properties, and multifaceted biological functions of GSTO1, and clarifies the potential mechanistic correlation between anesthetic/surgical stress-induced redox imbalance, neuroinflammation, and PND pathogenesis. We propose a verifiable three-axis regulatory framework centered on the Nrf2 antioxidant pathway, NF-κB inflammatory cascade, and NLRP3 inflammasome signaling. Circulating GSTO1 in serum and platelets, detectable via ELISA and enzymatic activity assays, is proposed as a novel minimally invasive peripheral biomarker for preoperative cognitive risk stratification and central redox status evaluation. Furthermore, we differentiate context-dependent GSTO1-targeted intervention strategies, replacing vague universal modulator concepts with stage-specific therapeutic regimens for acute perioperative injury and chronic neurodegeneration. This review provides innovative theoretical foundations and targeted translational prospects for mechanistic research and clinical neuroprotective strategies against PND.