AUTHOR=Li Wei-Qi , Yang Jia-Hua , Liu Lu-Lu , Ding Song-Tao , Yu Bin , Jiang Lin , Yan Ning , Liu Han-Deng TITLE=Exercise as a multitarget therapy: modulating myokines, neurotrophins, and inflammation in Parkinson’s disease JOURNAL=Frontiers in Aging Neuroscience VOLUME=Volume 17 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1580029 DOI=10.3389/fnagi.2025.1580029 ISSN=1663-4365 ABSTRACT=Parkinson’s disease is a progressive neurodegenerative disorder characterized by degeneration of dopaminergic neurons, leading to significant motor and non-motor symptoms. Recent studies emphasize that exercise is a beneficial intervention, not only helping to decrease the risk of developing of Parkinson’s disease but also alleviating existing symptoms. This review investigates the mechanisms by which exercise influences myokines, neurotrophic factors, growth factors, and inflammation-related factors to promote neuronal survival and plasticity in Parkinson’s disease. Despite promising findings, the specific molecular pathways through which exercise exerts neuroprotective effects remain largely unexplored, and individual variability in disease progression necessitates personalized exercise interventions tailored to each patient’s needs. Furthermore, for patients unable to engage in physical activity, exploring alternative therapies that mimic exercise to achieve neuroprotective effects is crucial. In conclusion, this review highlights the need for further research to elucidate the molecular mechanisms of exercise-induced neuroprotection and to establish effective individualized exercise programs, ultimately improving the management of Parkinson’s disease.