Shahid Ishaq ¹ Iqbal Ali Shah ¹ Shin-Da Lee ^1* Bor-Tsang Wu ^2*

• ¹ PhD program in Healthcare Science, China Medical University, Taichung, Taiwan
• ² National Taichung University of Science and Technology, Taichung, Taiwan

This systematic review aimed to summarize the effects of various exercise training regimens on protein or genes expression within the nigrostriatum and their role in neuroprotection and motor function improvement in animal models of Parkinson's disease (PD). PubMed, EMBASE and Web of Science were searched up to June 2024 and included sixteen studies that adhere to PRISMA guidelines and CAMARADES checklist scores ranging from 4 to 6 out of 10. Various exercise training regimens, administered 5 days per week for 6.5 weeks, were applied to MPTP, 6-OHDA, and PFF-α-synuclein-induced PD animal models. Exercise training was found to downregulate the inflammatory pathway by attenuating α-synuclein aggregation, inhibiting the TLR/MyD88/IκBα signaling cascade and NF-κB phosphorylation, and decreasing pro-inflammatory cytokines IL-1β and TNF-α while increasing antiinflammatory cytokines IL-10 and TGF-β within the nigrostriatum. It also inhibited the ASC and NLRP3 inflammasome complex and reduced the BAX/Bcl-2 ratio and caspase-1/3 proteins, thereby decreasing neuronal apoptosis in the nigrostriatum. Exercise training elevated the expression of Pro-BDNF, BDNF, GDNF, TrkB, and Erk1/2, providing neurotrophic support to dopaminergic neurons. Furthermore, it upregulated the dopaminergic signaling pathway by increasing the expression of TH, DAT, PSD-95, and synaptophysin in the nigrostriatum. These findings suggest that exercise training downregulates inflammatory and apoptotic pathways while upregulating BDNF/GDNF and dopaminergic signaling pathways within the nigrostriatum, thereby limiting dopaminergic neuron loss, preventing neurodegeneration, and improving motor performance.