{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:48:03Z","timestamp":1782362883525,"version":"3.54.5"},"reference-count":271,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"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. Neurol."],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and persistent motor and non-motor impairment. Exercise has emerged as a promising and helpful adjunctive strategy for PD because it improves functional outcomes and may engage biological processes related to neuroprotection and neuroplasticity. Among these mechanisms, brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) signaling have received increasing attention. This review summarizes pathological alterations of BDNF\/TrkB signaling in PD and evaluates how exercise may influence this system to support neuronal survival, synaptic plasticity, and microenvironmental homeostasis. Evidence from animal studies suggests that the phosphoinositide 3-kinase\/Akt (PI3K\/Akt) and mitogen-activated protein kinase\/extracellular signal-regulated kinase (MAPK\/ERK) pathways are mainly supported by preclinical PD exercise studies that assessed dopaminergic preservation, downstream pathway activation, and behavioral recovery. In contrast, phospholipase C\u03b3 (PLC\u03b3)-related signaling, TrkB isoform-specific regulation, astrocyte-dependent mechanisms, and trophic trafficking remain less clearly defined. This review also emphasizes key translational gaps, including peripheral BDNF biomarker limitations, the mismatch between human biomarker studies and animal mechanistic studies, and the need to match exercise prescriptions with specific BDNF\/TrkB-related mechanisms.<\/jats:p>","DOI":"10.3389\/fneur.2026.1860227","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:21:56Z","timestamp":1782361316000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exercise modulation of BDNF\/TrkB signaling in Parkinson\u2019s disease: an evidence-calibrated review of neuroprotective mechanisms, biomarker limitations, and translational gaps"],"prefix":"10.3389","volume":"17","author":[{"given":"Chuan","family":"Chen","sequence":"first","affiliation":[{"name":"Jishou University","place":["Jishou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaihua","family":"Liu","sequence":"additional","affiliation":[{"name":"Jishou University","place":["Jishou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Physical Education and Arts, Hunan University of Medicine","place":["Huaihua, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Changsha Preschool Education College","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"7135","DOI":"10.3390\/ijms22137135","article-title":"Possible link between SARS-CoV-2 infection and Parkinson\u2019s disease: the role of toll-like receptor 4","volume":"22","author":"Conte","year":"2021","journal-title":"Int J Mol Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.3390\/biomedicines11051240","article-title":"Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systems","volume":"11","author":"Marques","year":"2023","journal-title":"Biomedicine"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s40035-023-00378-6","article-title":"Role of dopamine in the pathophysiology of Parkinson\u2019s disease","volume":"12","author":"Zhou","year":"2023","journal-title":"Transl Neurodegener"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1197853","DOI":"10.3389\/fnmol.2023.1197853","article-title":"Alpha synuclein post translational modifications: potential targets for Parkinson\u2019s disease therapy?","volume":"16","author":"Brembati","year":"2023","journal-title":"Front Mol Neurosci"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"620","DOI":"10.3390\/brainsci14060620","article-title":"A computational model of deep brain stimulation for Parkinson\u2019s disease tremor and bradykinesia","volume":"14","author":"Nair","year":"2024","journal-title":"Brain Sci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1007\/s10787-023-01259-0","article-title":"Neuromodulation in Parkinson\u2019s disease targeting opioid and cannabinoid receptors, understanding the role of NLRP3 pathway: a novel therapeutic approach","volume":"31","author":"Alam","year":"2023","journal-title":"Inflammopharmacology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e70540","DOI":"10.1111\/cns.70540","article-title":"Levodopa and plant-derived bioactive compounds in Parkinson\u2019s disease: mechanisms, efficacy, and future perspectives","volume":"31","author":"Akta\u015f","year":"2025","journal-title":"CNS Neurosci Ther"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"3054","DOI":"10.1007\/s12035-023-03257-3","article-title":"Adenosinergic pathway in Parkinson\u2019s disease: recent advances and therapeutic perspective","volume":"60","author":"Zhao","year":"2023","journal-title":"Mol Neurobiol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"478","DOI":"10.4103\/1673-5374.350193","article-title":"Combined cell-based therapy strategies for the treatment of Parkinson\u2019s disease: focus on mesenchymal stromal cells","volume":"18","author":"Rodr\u00edguez-Pallares","year":"2023","journal-title":"Neural Regen Res"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1093\/brain\/awae365","article-title":"Lewy pathology formation in patient-derived GBA1 Parkinson\u2019s disease midbrain organoids. 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