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Background <p>The diagnosis of Parkinson’s disease (PD) is currently clinical. While CSF-based α-synuclein Real-time quaking-induced conversion (RT-QuIC) assays have shown promising diagnostic performance in sporadic PD, accessible blood-based biomarkers for early diagnosis, prognosis, and disease monitoring remain limited. Evidence suggests that microRNAs in Extracellular vesicles (EV) are stable in circulation and may reflect disease-associated dysregulation.</p> Objective <p>To identify a panel of dysregulated EV-microRNAs that are linked to PD pathogenesis and to validate them in plasma EVs.</p> Methods <p>Dysregulated miRNAs in PD were identified from GEO datasets and from published high-throughput next-generation sequencing (NGS) data on plasma EV. Based on recurrence and biological relevance, five miRNAs were selected for validation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using Funrich, Enrichr, and Database for Annotation, Visualization and Integrated Discovery (DAVID), and further target gene analysis for hub genes was performed using Cytoscape. qRT-PCR was used for the validation of selected miRNAs.</p> Results <p>Comparative analysis of miRNAs in PD revealed 89 unique miRNAs. Integrated target prediction yielded 36 genes, among which the top 10 hub genes were identified using the protein-protein interaction network. KEGG and GO enrichment analyses indicate that the predicted target genes were significantly associated with cell-cell adhesion, endoplasmic reticulum protein processing, apoptosis, cellular senescence, and key pathways such as p53, MAPK, and FOXO signaling. RT-PCR revealed significant increase in hsa-let-7e-5p, hsa-miR-19b-3p, hsa-miR-24-3p and hsa-miR-331-5p in PD.</p> Conclusion <p>The EV miRNAs, specifically, hsa-let-7e-5p, hsa-miR-19b-3p, hsa-miR-24-3p, and hsa-miR-331-5p are promising candidates for PD diagnosis as they are associated with regulatory pathways involved in PD pathogenesis.</p>

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Identification and validation of Parkinson’s disease relevant microRNAs in plasma extracellular vesicles

  • 期刊论文

  • 发表日期：

    2026年8月1日

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  • Deepthy Chandran,
  • Syam Krishnan,
  • Srinivas Gopala,
  • Madhusoodanan Urulangodi

摘要

Background

The diagnosis of Parkinson’s disease (PD) is currently clinical. While CSF-based α-synuclein Real-time quaking-induced conversion (RT-QuIC) assays have shown promising diagnostic performance in sporadic PD, accessible blood-based biomarkers for early diagnosis, prognosis, and disease monitoring remain limited. Evidence suggests that microRNAs in Extracellular vesicles (EV) are stable in circulation and may reflect disease-associated dysregulation.

Objective

To identify a panel of dysregulated EV-microRNAs that are linked to PD pathogenesis and to validate them in plasma EVs.

Methods

Dysregulated miRNAs in PD were identified from GEO datasets and from published high-throughput next-generation sequencing (NGS) data on plasma EV. Based on recurrence and biological relevance, five miRNAs were selected for validation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using Funrich, Enrichr, and Database for Annotation, Visualization and Integrated Discovery (DAVID), and further target gene analysis for hub genes was performed using Cytoscape. qRT-PCR was used for the validation of selected miRNAs.

Results

Comparative analysis of miRNAs in PD revealed 89 unique miRNAs. Integrated target prediction yielded 36 genes, among which the top 10 hub genes were identified using the protein-protein interaction network. KEGG and GO enrichment analyses indicate that the predicted target genes were significantly associated with cell-cell adhesion, endoplasmic reticulum protein processing, apoptosis, cellular senescence, and key pathways such as p53, MAPK, and FOXO signaling. RT-PCR revealed significant increase in hsa-let-7e-5p, hsa-miR-19b-3p, hsa-miR-24-3p and hsa-miR-331-5p in PD.

Conclusion

The EV miRNAs, specifically, hsa-let-7e-5p, hsa-miR-19b-3p, hsa-miR-24-3p, and hsa-miR-331-5p are promising candidates for PD diagnosis as they are associated with regulatory pathways involved in PD pathogenesis.