miR-126-5p and miR-543 in Parkinson's disease: Insights into diagnosis and symptom correlation

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder globally, predominantly affecting people over 50 and characterized by symptoms like tremor and bradykinesia due to the degeneration of dopaminergic neurons. During PD progression, extracellular vesicles (EVs) carry biomolecules that reflect the disease state and transfer their cargo to recipient cells, potentially worsening the condition. MiRNAs within EVs may help distinguish disease stages, evaluate progression, and guide individualized treatment options. This study aimed to evaluate the expression levels of EV miRNAs in the blood serum of PD patients to differentiate between healthy individuals and PD patients with varying disease severity. EV miRNAs were isolated from blood serum, transcribed into cDNA, and quantified using RT-PCR. miRNA expression profiles were analyzed in 20 healthy controls (HC) and 88 Parkinson’s disease (PD) patients. We compared HC and PD groups and examined associations between miRNA expression and symptom severity, including bradykinesia, tremor, rigidity, dyskinesia, gait disturbances, nocturnal akinesia, the "on-off" phenomenon, orthostatic hypotension, as well as disease onset and duration. Long-term miRNA expression changes were also evaluated in patients undergoing gamma knife surgery (n=5) and deep brain stimulation (n=9) as treatments for PD. Statistical analyses were performed using GraphPad Prism 8. We identified significant differences in EV miR-126-5p and miR-543 expression among patient groups. ROC analysis demonstrated that the combination of miR-126-5p and miR-543 effectively differentiated PD patients from healthy controls, with an AUC of 0.982 (p<0.001). In PD patients, miR-126-5p was upregulated, whereas miR-543 was downregulated compared to healthy controls. Moreover, increased miR-126-5p expression correlated with greater severity of bradykinesia, orthostatic hypotension, and cognitive impairment (p<0.05). miR-543 expression was elevated in patients with more severe nocturnal akinesia but decreased in those with orthostatic hypotension (p<0.05). Disease onset and duration had no significant effect on miR-126-5p or miR-543 expression. Regarding surgical treatments, gamma knife surgery did not alter miRNA expression, while deep brain stimulation significantly increased miR-543 levels (p<0.05), suggesting a potential link between higher miR-543 expression and improved disease outcomes. In conclusion, the work demonstrates the importance of miRNA molecules in the context of PD. More detailed miRNA studies could be valuable in clinical practice for early PD diagnosis, enabling timely treatment and tracking disease progression.