AUTHOR=Liu Chang , He Wei , Zhang JianHua TITLE=Exercise regulates mitophagy to alleviate parkinsonian neurodegeneration JOURNAL=Frontiers in Aging Neuroscience VOLUME=Volume 17 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1678460 DOI=10.3389/fnagi.2025.1678460 ISSN=1663-4365 ABSTRACT=Parkinson’s disease (PD) is a common neurodegenerative disorder with a rising incidence in aging populations, substantially diminishing patients’ quality of life. Mitochondria are central to neuronal energy metabolism, and mitophagy plays a pivotal role in maintaining mitochondrial quality by removing damaged organelles. In PD, impaired mitophagy leads to the accumulation of dysfunctional mitochondria, exacerbating oxidative stress and bioenergetic deficits and thereby accelerating disease progression. In recent years, exercise has emerged as a safe and cost-effective intervention that alleviates PD symptoms. Exercise can activate mitophagy through key signaling pathways—including AMP-activated protein kinase (AMPK)/Unc-51–like kinase 1 (ULK1) and PTEN-induced kinase 1 (PINK1)/Parkin—thereby enhancing mitochondrial function and antioxidant capacity. This review synthesizes current evidence on how exercise modulates mitophagy to confer neuroprotection in PD, providing conceptual and practical insights for non-pharmacological management strategies in neurodegenerative disease.