{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:37:21Z","timestamp":1789508241649,"version":"build-2803163510"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"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), the most prevalent form of dementia, is characterized by progressive memory impairment and cognitive dysfunction. The neuropathological hallmarks of this neurodegenerative disorder encompass two principal pathological features: extracellular deposition of amyloid-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (A\u03b2) plaques due to abnormal protein aggregation, and intracellular accumulation of neurofibrillary tangles (NFTs) caused by hyperphosphorylation of tau proteins (p-Tau). These pathological changes induce synaptic loss and neuronal apoptosis, which leads to impaired neuroplasticity and progressive deterioration of cognitive function. Autophagy, a critical mechanism in the central nervous system (CNS) responsible for clearing misfolded protein aggregates and damaged organelles, plays a pivotal role in maintaining neuronal homeostasis and synaptic plasticity. However, AD is associated with autophagy impairment, resulting in the accumulation of toxic protein aggregates and damaged organelles. These pathological changes disrupt protein homeostasis, thereby exacerbating neurodegenerative processes. Currently, AD therapeutic strategies remain limited. Emerging evidence indicates that exercise intervention mitigates cognitive decline and enhances synaptic plasticity, potentially through reducing A\u03b2 deposition and pathological phosphorylation of tau proteins. However, the precise mechanisms through which these interventions act remain to be fully elucidated. Recent studies have shown that exercise can promote autophagosome formation, fusion, and lysosomal hydrolytic function, thereby ameliorating the pathological progression of AD. Despite these promising findings, the precise molecular targets and underlying signaling mechanisms through which exercise modulates autophagy in AD remain to be fully elucidated. The purpose of this study is to establish innovative therapeutic targets while identifying mechanistically actionable pharmacological targets to advance therapeutic development against AD pathogenesis.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2026.1780247","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:50:24Z","timestamp":1773298224000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular mechanisms underlying exercise-enhanced autophagy in improving neuroplasticity in Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Qian","family":"Li","sequence":"first","affiliation":[{"name":"Department of Sports Human Sciences, College of Physical Education, Yangzhou University","place":["Yangzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renqing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Sports Human Sciences, College of Physical Education, Yangzhou University","place":["Yangzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Sports Human Sciences, College of Physical Education, Yangzhou University","place":["Yangzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haocheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Physiology, SUNY Upstate Medical University","place":["Syracuse, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1131214","DOI":"10.3389\/fnins.2023.1131214","article-title":"The effects of resistance exercise on cognitive function, amyloidogenesis, and neuroinflammation in Alzheimer's disease","volume":"17","author":"Azevedo","year":"2023","journal-title":"Front. 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