MicroRNA targeted gene regulation in salivary gland tissue of de novo idiopathic Parkinson disease patient

ImportanceBiomarkers for Parkinson disease (PD) patients are essential for accurate diagnosis and treatment. However, as of the present, no specific molecules have been defined for this purpose. While alpha-synucleinopathy has been confirmed in the submandibular gland (SMG) tissue of PD patients, in-depth disease-related molecular studies, such as tissue-specific transcriptional signals, have not been thoroughly explored.ObjectivesTo investigate disease-relevant tissue-specific transcriptional signals in submandibular gland tissue from PD patients, with the aim of identifying potential diagnostic, prognostic, and pathophysiologic biomarkers.Design, setting, and participantsThis case-control study was conducted at a university affiliated tertiary hospital. A total of seven PD patients and six age- and sex-matched individuals without neurological diseases were enrolled between October 2022 and April 2023. SMG tissue was obtained via core needle biopsy, and blood samples were collected from each participant. Total RNA sequencing (RNA-seq) and total small RNA sequencing were performed on these samples, with a total of 26 RNA-seq and 26 small RNA-seq samples used for the final analysis.Main outcomes and measuresDetection of differentially expressed genes and miRNAs in SMG and in blood from PD patients, and analyze their functional integration.ResultsMost of the highest terms in gene ontology analysis of DEGs in PD patients were related to cytokine-related inflammation, immune response, cellular membrane, or secretory granule-related functions. The KEGG pathway analysis revealed that these DEGs interacted with cytokine, inflammation, and immune-related pathways. Synphilin-1 expression was significantly downregulated in SMG of PD patients, while alpha-synuclein expression was not significantly different between both groups in both types of samples.We identified 15 tissue-specific miRNA signals in SMG that showed better diagnostic ability compared to those in blood samples. The correlation between DEGs and environmental factors appeared to be altered in PD patients.Conclusions and relevanceOur findings suggest that the DEGs and miRNA signatures identified in SMG tissue may serve as promising diagnostic and prognostic biomarkers. These molecular insights offer potential avenues for the development of novel therapeutic strategies targeting the underlying disease mechanisms in PD patients.