{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:59:59Z","timestamp":1790935199159,"version":"4.1.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>\n                    Alzheimer\u2019s disease (AD) is a neurodegenerative disorder characterized by extracellular deposition of amyloid-\u03b2 (A\u03b2), intracellular hyperphosphorylation of microtubule-associated protein tau and chronic neuroinflammation. At present, effective disease-modifying therapies for AD remain limited. Dexmedetomidine (Dex), a highly selective \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    -adrenergic receptor agonist, has been reported in recent years to exert significant neuroprotective effects. Accumulating evidence indicates that Dex may ameliorate AD pathology through multiple mechanisms. In terms of A\u03b2 metabolism, Dex reduces A\u03b2 production by downregulating \u03b2-site amyloid precursor protein-cleaving enzyme 1 (BACE1) expression. With respect to tau pathology, Dex may counteract abnormal tau hyperphosphorylation in AD-related models, although relatively high experimental doses have also been associated with increased tau phosphorylation. Regarding immune regulation, Dex attenuates neuroinflammatory signaling by inhibiting NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and related pro-inflammatory pathways. In addition, Dex modulates neurotrophic support, ferroptosis, autophagic flux, and synaptic homeostasis. These multitarget effects have been observed across heterogeneous preclinical models and dose ranges; however, an AD-specific therapeutic window and long-term safety profile remain to be established. This narrative review synthesizes the available preclinical evidence on the multitarget actions of Dex in AD-related models and critically evaluates dose dependence, pharmacokinetic and safety considerations, and current translational limitations.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2026.1952923","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:46:12Z","timestamp":1790934372000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dexmedetomidine as a potential neuroprotective agent against Alzheimer\u2019s disease: molecular mechanisms and therapeutic perspectives"],"prefix":"10.3389","volume":"18","author":[{"given":"Jun","family":"Kang","sequence":"first","affiliation":[{"name":"First Clinical Medical College of Lanzhou University","place":["Lanzhou, China"]},{"name":"Department of Anesthesiology, Gansu Provincial Hospital","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbo","family":"Duan","sequence":"additional","affiliation":[{"name":"First Clinical Medical College of Lanzhou University","place":["Lanzhou, China"]},{"name":"Department of Anesthesiology, Gansu Provincial Hospital","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxuan","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Gansu Provincial Hospital","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangping","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Research and Translational Medicine, Gansu Provincial Hospital","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Yan","sequence":"additional","affiliation":[{"name":"First Clinical Medical College of Lanzhou University","place":["Lanzhou, China"]},{"name":"Department of Anesthesiology, Gansu Provincial Hospital","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jalz.2012.02.001","article-title":"2012 Alzheimer's disease facts and figures","volume":"8","year":"2012","journal-title":"Alzheimers Dement."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"6926","DOI":"10.1523\/JNEUROSCI.0800-08.2008","article-title":"Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease","volume":"28","author":"Boland","year":"2008","journal-title":"J. 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