The neuroprotective effects of Dexmedetomidine: key mechanisms focusing on neuronal programmed cell death

In the central nervous system (CNS), programmed cell death (PCD) of neurons, is precisely regulated by various biomolecules to maintain neuronal development, establish neural structures, and maintain CNS homeostasis. Under the stimulation of pathologic factors, the abnormal cascade of PCD signals leads to irreversible damage to neuronal cells, resulting in the occurrence and progression of neurological deficits and neurodegenerative diseases (NDDs). Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist, is widely used for relieving anxiety, sedation, and pain management in clinical anesthesia and critical care. A growing body of research confirms that DEX has neuroprotective effects, including reducing postoperative agitation and pain, protecting the blood–brain barrier, maintaining hemodynamic stability, minimizing neuronal damage, and alleviating neuroinflammation and oxidative stress. In this study, we will summarize the neuroprotective effects of DEX in various CNS diseases, with a focus on its regulatory role and molecular mechanisms in neuronal PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy, and parthanatos. We also explored the therapeutic potential of PCD as a target and strategy to underpin the neuroprotective effects of DEX.