{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T06:11:41Z","timestamp":1777961501906,"version":"3.51.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005227","name":"Jilin Provincial Department of Health","doi-asserted-by":"publisher","award":["No. 482022118"],"award-info":[{"award-number":["No. 482022118"]}],"id":[{"id":"10.13039\/501100005227","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["YDZJ202201ZYTS158"],"award-info":[{"award-number":["YDZJ202201ZYTS158"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      Mitochondrial dysfunction and oxidative stress are key contributors to the progression of Alzheimer\u2019s disease (AD). Salidroside, a bioactive glycoside derived from\n                      <jats:italic>Rhodiola rosea<\/jats:italic>\n                      , exhibits neuroprotective and antioxidative properties; however, its effects on mitochondrial dysfunction and APP processing in AD remain to be fully elucidated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and study design<\/jats:title>\n                    <jats:p>\n                      We employed both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      models to evaluate the neuroprotective potential of salidroside. D-galactose-induced AlCl3 exposed aging mouse model was used for behavioral assessments, biochemical analyses of brain tissue biomarkers, and evaluation of mitochondrial dysfunction-related proteins and functions.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments with HT-22 hippocampal neurons assessed the effects of salidroside on oxidative stress, mitochondrial integrity, apoptosis, and amyloid precursor protein (APP) processing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Salidroside significantly improved cognitive performance and reduced A\u03b2 deposition in the AlCl3 exposed aging mouse by modulating APP processing, characterized by downregulation of \u03b2- and \u03b3-secretase activities and enhancement of \u03b1-secretase activity. These changes coincided with decreased mitochondrial protein aggregation and restored mitochondrial function and redox balance.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , salidroside attenuated reactive oxygen species (ROS) generation, inhibited neuronal apoptosis, and suppressed A\u03b2 production, demonstrating broad neuroprotective effects relevant to AD pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest that salidroside may alleviate mitochondrial dysfunction and reduce mitochondrial protein aggregation by modulating APP processing, promoting sAPP\u03b1 production while decreasing \u03b2-CTF and A\u03b2 levels. These findings provide preliminary evidence supporting the neuroprotective potential of salidroside in ameliorating mitochondrial impairment and cognitive deficits associated with Alzheimer\u2019s disease, warranting further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnbeh.2026.1802923","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:31:54Z","timestamp":1777959114000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Salidroside mitigates cognitive deficits in AlCl3 exposed aging mouse by modulating APP processing and mitochondrial dysfunction"],"prefix":"10.3389","volume":"20","author":[{"given":"Yiru","family":"Dong","sequence":"first","affiliation":[{"name":"Neurotoxicology Laboratory, Department of Preventive Medicine, Yanbian University, Yanji","place":["Jilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiling","family":"Jin","sequence":"additional","affiliation":[{"name":"Neurotoxicology Laboratory, Department of Preventive Medicine, Yanbian University, Yanji","place":["Jilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Neurotoxicology Laboratory, Department of Preventive Medicine, Yanbian University, Yanji","place":["Jilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanji","family":"Xu","sequence":"additional","affiliation":[{"name":"Neurotoxicology Laboratory, Department of Preventive Medicine, Yanbian University, Yanji","place":["Jilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"102119","DOI":"10.1016\/j.arr.2023.102119","article-title":"Evaluation and targeting of amyloid precursor protein (APP)\/amyloid beta (A\u03b2) axis in amyloidogenic and non-amyloidogenic pathways: a time outside the tunnel.","volume":"92","author":"Al-Kuraishy","year":"2023","journal-title":"Ageing Res. 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