{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:16:15Z","timestamp":1788441375754,"version":"build-2803163510"},"reference-count":46,"publisher":"IMR Press","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation for the Scientific Research Institute of Neurosciences and Medicine","award":["theme no. 126020316369-9 (2026\u22122028)"],"award-info":[{"award-number":["theme no. 126020316369-9 (2026\u22122028)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background:Trehalose (TRE) has demonstrated neuroprotective potential in models of Alzheimer's disease (AD)-like pathology and has been shown to activate AMP-activated protein kinase (AMPK) and induce autophagy in hepatocytes. The molecular mechanisms underlying the neuroprotective effects of TRE in the brain, including the involvement of AMPK signaling and autophagy, remain unclear. Methods:AD was modeled in C57BL\/6 mice by intracerebroventricular administration of the amyloid-\u03b2 (A\u03b2) fragment A\u03b2(25\u201335). The effects of TRE treatment (a 3% water solution in drinking water for 20 days) on AD-like pathology in the brain (frontal cortex, amygdala, and hippocampus) were assessed by immunohistochemical analysis, while cognitive function was evaluated using the passive avoidance test. AMPK activation was assessed by measuring AMPK (p-AMPK) levels in the brain and by evaluating the effects of its inhibitor dorsomorphin (DM; 10 mg\/kg, i.p., 20 days, every other day for 20 days).Results:A\u03b2-treated mice exhibited markedly increased A\u03b2 levels and neuroinflammatory responses in the brain, whereas levels of the autophagy marker LC3-II and p-AMPK were moderately reduced. TRE markedly reduced A\u03b2 accumulation and neuroinflammation and restored cognitive performance to levels comparable to those of the Control group; it also increased LC3-II immunoreactivity and p-AMPK levels in the hippocampus and amygdala. DM did not abolish the neuroprotective effects of TRE but moderately inhibited AMPK in the hippocampus.Conclusions:Marked changes in brain A\u03b2 levels and cognitive performance were not associated with either p-AMPK or autophagy marker levels, suggesting that additional mechanisms contribute to the neuroprotective effects of TRE in AD. Markers of autophagy initiation and AMPK activity responded similarly to AD modeling and TRE treatment and were positively correlated in the hippocampus, suggesting a role for AMPK in the regulation of TRE-induced hippocampal autophagy.<\/jats:p>","DOI":"10.31083\/fbl53657","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:35:31Z","timestamp":1788438931000},"source":"Crossref","is-referenced-by-count":0,"title":["Role of AMPK Signaling in the Neuroprotective Effects of Trehalose in Mice With a Pharmacological Model of Alzheimer\u2019s Disease"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0957-7618","authenticated-orcid":true,"given":"Alexander B.","family":"Pupyshev","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Neuroscience, Scientific Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina V.","family":"Ovsyukova","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neuroscience, Scientific Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna A.","family":"Akopyan","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neuroscience, Scientific Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V.","family":"Tenditnik","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neuroscience, Scientific Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana A.","family":"Korolenko","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neuroscience, Scientific Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina I.","family":"Dubrovina","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neuroscience, Scientific Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Tikhonova","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neuroscience, Scientific Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Hansson O. 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