{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:00:18Z","timestamp":1783400418142,"version":"3.54.6"},"reference-count":222,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"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>Parkinson\u2019s disease (PD) is characterized by the progressive degeneration of midbrain dopaminergic neurons, with apoptosis representing the predominant mechanism of neuronal cell death among the various forms of cell death implicated in PD. The lack of effective strategies to inhibit neuronal apoptosis remains a major challenge in PD management, particularly given the limitations associated with current pharmacological interventions. Exercise has gained increasing attention as a potentially effective approach to reduce PD symptoms and may alter disease progression by regulating apoptosis. However, the exact molecular pathways by which exercise provides neuroprotective benefits in PD remain incompletely understood. This narrative review synthesizes current evidence from animal models and human studies on the molecular mechanisms by which exercise alleviates neuronal apoptosis in PD. Following a comprehensive literature search of PubMed, Web of Science, and Scopus databases, we critically evaluate the evidence for exercise-mediated regulation of three key interconnected pathways: mitochondrial function (AMPK\/Sirt1\/PGC-1\u03b1 signaling), neuroinflammation (TLR\/MyD88\/NF-\u03baB signaling), and autophagy (CaMKII\/Beclin1\/p62 signaling). We discuss the translational limitations of current animal studies, identify gaps in the literature including the predominance of treadmill-based protocols and limited human evidence, and propose an integrative framework linking these pathways to coordinated neuroprotection. Understanding these molecular interactions will inform the development of optimized, personalized exercise interventions for PD management.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1810397","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:41:27Z","timestamp":1774593687000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Exercise suppresses apoptosis for alleviating Parkinson\u2019s disease: effects on pathophysiological molecular pathways"],"prefix":"10.3389","volume":"18","author":[{"given":"Junfei","family":"Chen","sequence":"first","affiliation":[{"name":"Jiangsu Research Institute of Sports Science","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Physical Education, Yangzhou University","place":["Yangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Physical Education, Yangzhou University","place":["Yangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Physical Education, Yangzhou University","place":["Yangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Research Institute of Sports Science","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/s41572-021-00286-x","article-title":"Parkinson disease-associated cognitive impairment","volume":"7","author":"Aarsland","year":"2021","journal-title":"Nat. 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