Objective: This study aims to  analyze the shared molecular pathways between Parkinson’s disease (PD) and constipation through integrative bioinformatics methodologies and further validate candidate biomarkers in a vitro and in vivo models.

Background: PD and constipation are strongly associated, with up to 90% of PD patients experiencing constipation, which also serves as a prodromal indicator and risk factor for the disease. Emerging evidence suggests that their relationship stems from shared molecular mechanisms linked to gut-brain axis dysfunction, potentially representing a unifying pathological process. Understanding this interplay could pave the way for novel therapeutic interventions targeting both conditions.

Method: Differentially expressed genes (DEGs) were identified via the R limma package, and Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify hub modules. Biological enrichment analysis was performed on these candidate DEGs to elucidate the involved biological processes. A gene-gene interaction (GGI) network was constructed to identify shared hub biomarkers. We validated candidate biomarkers’ expression in vitro using α-synuclein (α-syn)-treated SH-SY5Y cells and in vivo employing an α-syn-induced PD mouse model and loperamide-induced constipation model.

Results: Numerous DEGs were identified in both conditions, with 14 shared DEGs found through the intersection of core modules and upregulated DEGs. Biological enrichment analysis revealed that these DEGs are primarily involved in energy metabolism, protein modification, and mitochondrial function. We identified five key hub genes using the GGI network and gene topological analysis. Notably, SHMT2 expression was significantly upregulated after α-syn treatment in vitro. Immunohistochemical analysis revealed a notable increase in SHMT2 expression within brain tissues and colon tissues (p < 0.001) in the PD mouse model compared to controls. Similar increases in SHMT2 expression levels were observed in the colon of the constipation model.

Conclusion: Our findings provide novel insights into the molecular mechanisms linking PD and constipation, highlighting SHMT2 as a promising biomarker and potential therapeutic target for managing both motor and non-motor symptoms of PD.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-insights-into-the-association-between-parkinsons-disease-and-constipation-role-of-shmt2-as-a-promising-biomarker/