Dexmedetomidine attenuates Alzheimer’s pathogenesis by targeting the ROS-mediated XIAP-MDM2-p53 signaling axis

Introduction: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with a complex pathological process, in which oxidative stress serves as a key pathogenic mechanism. Studies have shown that the anesthetic adjuvant dexmedetomidine (Dex) can improve postoperative cognitive function in AD patients. This study aimed to explore whether dexmedetomidine alleviates AD-associated neuronal apoptosis and cognitive impairment via reducing overproduction of ROS and regulating the XIAP signaling pathway. Methods: cognitive deficits and brain pathology were evaluated in AD model mice using Morris water maze tests and immunofluorescence staining. Results: results indicated that dexmedetomidine improved cognitive deficits and intervened in AD pathology in the hippocampal region of AD model mice. Conclusion: This study reveals that dexmedetomidine inhibits ROS release and activates the XIAP-MDM2-p53 signaling pathway, thereby delaying apoptosis and ameliorating cognitive impairment in AD progression.