Extracellular vesicle derived miR-101-3p and miR-30b-5p as indicators of Parkinson’s disease progression

Abstract

Parkinson’s disease (PD) is a chronic neurodegenerative disorder primarily affecting movement due to the progressive degeneration of dopaminergic neurons. It is characterized by motor symptoms such as tremors, bradykinesia and rigidity, which worsen over time. Extracellular vesicles (EVs) facilitate intercellular communication by transporting biomolecules, including microRNAs (miRNAs), which may reflect disease state and progression. Changes in EV miRNA expression could serve as valuable biomarkers for assessing PD severity and guiding treatment approaches. This study investigated the expression levels of specific EV miRNAs in the blood serum of PD patients at different stages of disease severity. EV miRNAs were extracted from blood serum, converted into cDNA, and analyzed using RT-PCR. The study included 88 PD patients with varying symptom severity. miRNA expression was assessed in relation to motor impairments such as bradykinesia, tremor, rigidity, dyskinesia, gait disturbances, and the "on-off" phenomenon, as well as disease onset and duration. Statistical analysis was conducted using GraphPad Prism 8. Among the analyzed EV miRNAs, miR-101-3p and miR-30b-5p showed a significant decline in expression as motor symptoms worsened. Patients experiencing more severe bradykinesia, tremor, balance, "on-off" phenomenon and gait difficulties exhibited the most pronounced downregulation of these miRNAs. Statistical analysis revealed a strong negative correlation between miRNA expression and general motor symptom severity, with miR-101-3p showing r = - 0.362 (p < 0.01) and miR-30b-5p exhibiting r = -0.411 (p < 0.001). However, no significant association was observed between miRNA expression and disease onset or duration. This study suggests that EV miRNAs could serve as biomarkers for Parkinson’s disease severity. The downregulation of miR-101-3p and miR-30b-5p correlates with worsening symptoms, highlighting their potential in disease monitoring and targeted treatment strategies.