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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 \u03b12-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\u2013brain 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.<\/jats:p>","DOI":"10.3389\/fneur.2026.1762900","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:24:29Z","timestamp":1777523069000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The neuroprotective effects of Dexmedetomidine: key mechanisms focusing on neuronal programmed cell death"],"prefix":"10.3389","volume":"17","author":[{"given":"Jinxin","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Operating Room, Tongjiang County People's Hospital","place":["Bazhong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Immunization Program Section, Tongjiang County Center for Disease Control and Prevention (CDC)","place":["Bazhong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"869","DOI":"10.4103\/NRR.NRR-D-24-01324","article-title":"Mechanistic insights of neuronal death and neuroprotective therapeutic approaches in stroke","volume":"21","author":"Li","year":"2026","journal-title":"Neural Regen Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.4103\/1673-5374.339475","article-title":"Spinal cord injury-induced cognitive impairment: a narrative review","volume":"17","author":"Alc\u00e1ntar-Garibay","year":"2022","journal-title":"Neural Regen Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.2174\/0118715273289222231219094225","article-title":"Potential neuroprotective role of neurotrophin in traumatic brain injury","volume":"23","author":"Yap","year":"2024","journal-title":"CNS Neurol Disord Drug Targets."},{"key":"B4","doi-asserted-by":"publisher","first-page":"5497046","DOI":"10.1155\/2020\/5497046","article-title":"Proteostasis failure in neurodegenerative diseases: focus on oxidative stress","volume":"2020","author":"H\u00f6hn","year":"2020","journal-title":"Oxid Med Cell Longev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pneurobio.2016.07.005","article-title":"Oxidative stress: a major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson's disease and Alzheimer's disease","volume":"147","author":"Jiang","year":"2016","journal-title":"Prog Neurobiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1038\/s12276-023-01078-x","article-title":"Diversity and complexity of cell death: a historical review","volume":"55","author":"Park","year":"2023","journal-title":"Exp Mol Med."},{"key":"B7","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/s41418-023-01153-w","article-title":"Apoptotic cell death in disease-current understanding of the NCCD 2023","volume":"30","author":"Vitale","year":"2023","journal-title":"Cell Death Differ."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1038\/cdd.2014.47","article-title":"Programmed cell death during neuronal development: the sympathetic neuron model","volume":"21","author":"Kristiansen","year":"2014","journal-title":"Cell Death Differ."},{"key":"B9","doi-asserted-by":"publisher","first-page":"9947","DOI":"10.3390\/ijms25189947","article-title":"Significance of programmed cell death pathways in neurodegenerative diseases","volume":"25","author":"Guo","year":"2024","journal-title":"Int J Mol Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"149861","DOI":"10.1016\/j.brainres.2025.149861","article-title":"Alzheimer's disease: a jigsaw puzzle comprised of different types of programmed cell death pieces","volume":"1865","author":"Wang","year":"2025","journal-title":"Brain Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.4103\/1673-5374.331539","article-title":"Do pyroptosis, apoptosis, and necroptosis (PANoptosis) exist in cerebral ischemia? 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