Exploring Potential Causal Links: How Parkinson’s Disease Brain Damage Impacts Liver Health–A Mendelian Randomization and Transcriptomic Study

Tingting Liu,1,2,* Qi Chen,3,* Haojie Wu,1 Jingwen Li,1 Meiyan Xian,1 Keke Lu,1,2 Chaoyang Zhu,1,2 Jianshe Wei1,2 1School of Life Sciences, Henan University, Kaifeng, People’s Republic of China; 2Translational Neuromedicine and Neurourology Center, Huaihe Hospital of Henan University, Kaifeng, People’s Republic of China; 3School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianshe Wei, Email [email protected]: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by slow movements, muscle rigidity, tremors, and changes in gait and posture. Clinical studies have demonstrated a close association between PD and liver disease, but most research has focused on the impact of liver disorders on brain damage in PD, and further exploration is needed to understand the pathways and mechanisms underlying liver damage in patients with PD.Methods: This study employs Mendelian Randomization (MR) and transcriptomic analysis to investigate the causal impact of PD-related brain damage on liver health, identifying serum metabolites (eg, cysteine) and shared immune-inflammatory pathways as mediators.Results: The study indicates that PD-related brain damage does indeed have an impact on liver metabolic function. PD-related brain damage may disrupt the concentration of cysteine, which, when elevated, can cause liver cell damage and oxidative stress. Additionally, PD-related brain damage may affect specific genes (such as NCF1, NCF, and SELPLG) involved in immune and inflammatory responses that lead to liver damage. Interestingly, the anti-PD drug, tolcapone, has notable therapeutic effects but also negatively affects specific genes, contributing to liver damage in patients with PD.Conclusion: This study reveals the mechanisms by which PD affects liver metabolism and proposes cysteine as a biomarker and therapeutic target for liver damage in PD. Furthermore, the impact of PD treatment drugs on liver function was also evaluated. These findings provide important insights for the development of future PD treatment strategies, and further clinical research is needed to validate and optimize clinical interventions to maximize treatment efficacy and minimize side effects in patients with PD.Keywords: Parkinson’s disease, chronic hepatitis, Mendelian randomization analysis, serum metabolites, cysteine