Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 7-10 million people globally. It presents with motor symptoms like bradykinesia, tremors, rigidity, and postural instability, along with non-motor issues such as anxiety and mood fluctuations. PD is characterized by the progressive loss of nigrostriatal neurons, α-synuclein protein aggregation, reduced tyrosine hydroxylase level, and impaired dopamine signaling. Neuroinflammation plays a key role in PD progression, with elevated pro-inflammatory cytokines promoting M1 microglial activation, which exacerbates neurodegeneration. Conversely, anti-inflammatory cytokines such as IL-10 and IL-4 help shift microglia to the neuroprotective M2 phenotype, reducing inflammation. Animal models show an imbalance with increased M1 and reduced M2 microglia. This study explored the neuroprotective effects of treadmill exercise in a rotenone-induced PD mouse model. After 21 days of exercise, behavioral impairments improved, as shown by open field tests, Rota-rod, and footprint analysis. Exercise also reduced pro-inflammatory cytokines
TNF-α, and IL-1β levels while increasing anti-inflammatory cytokines
IL-10, and IL-4. This shift correlated with decreased α-synuclein levels and increased tyrosine hydroxylase expression, indicating reduced neurodegeneration. These findings suggest that treadmill exercise can mitigate PD symptoms and pathology by modulating neuroinflammation and restoring dopaminergic function.