Differential expression of gut miRNAs in idiopathic Parkinson's disease
Anna Kurz1, Rohit Kumar2, Bernd H Northoff3
1Department of Neurology, Ludwig Maximilian University, Munich, Germany; Department of Translational Neurodegeneration, German Centre for Neurodegenerative Diseases (DZNE), Munich, Germany.
Objective:
In the present work, we aimed to investigate the expression of microRNAs (miRNAs) in routine colonic biopsies obtained from patients with idiopathic Parkinson's disease (PD) and to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression.
Methods:
Patients with PD (n = 13) and healthy controls (n = 17) were prospectively recruited to undergo routine colonic biopsies for cancer screening. Total RNA was extracted from the biopsy material and the expression of miRNAs was quantified by Illumina High-Throughput Sequencing.
Results:
Statistical analysis revealed a significant submucosal enrichment of the miRNA hsa-miR-486-5p in colonic biopsies from PD patients compared to the control subjects. The expression of miR-486-5p correlated with age and disease severity as measured by the UPDRS and Hoehn & Yahr scale. miRNA gene target analysis identified 301 gene targets that are affected by miR-486-5p. A follow-up associated target identification and pathway enrichment analysis further determined their role in distinct biological processes in the enteric nervous system (ENS).
Interpretation:
Our work demonstrates an enrichment of submucosal miR-486-5p in routine colonic biopsies from PD patients. Our results will support the examination of miR-486-5p as a PD biomarker and help to understand the significance of the miR-486-5p gene targets for PD onset and progression. In addition, our data will support the investigation of the molecular and cellular mechanisms of GI dysfunction in PD.
Insights
MicroRNA hsa-miR-486-5p is enriched in colonic biopsies of Parkinson's disease (PD) patients, suggesting its potential as a diagnostic biomarker and offering insights into PD pathogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Gastroenterology
Background:
- Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder with gastrointestinal manifestations.
- MicroRNAs (miRNAs) are implicated in various cellular processes and diseases.
Purpose of the Study:
- To investigate miRNA expression in colonic biopsies from PD patients.
- To assess the diagnostic value of miRNAs as biomarkers for PD.
- To explore the mechanistic role of miRNAs in PD onset and progression.
Main Methods:
- Prospective recruitment of PD patients (n=13) and healthy controls (n=17).
- Collection of routine colonic biopsies for RNA extraction.
- Quantification of miRNA expression using Illumina High-Throughput Sequencing.
Main Results:
- Significant submucosal enrichment of hsa-miR-486-5p in PD patient biopsies compared to controls.
- Correlation of miR-486-5p expression with age and PD severity (UPDRS, Hoehn & Yahr scale).
- Identification of 301 gene targets affected by miR-486-5p, involved in enteric nervous system processes.
Conclusions:
- Submucosal miR-486-5p enrichment in colonic biopsies is a potential PD biomarker.
- miR-486-5p gene targets provide insights into PD pathogenesis and GI dysfunction in PD.
- Further investigation of miR-486-5p can elucidate molecular mechanisms underlying PD.
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