Unlocking Parkinson's disease: the role of microRNAs in regulation, diagnosis, and therapy.

Parkinson's disease (PD), the second most prevalent neurodegenerative disorder globally, imposes substantial healthcare burdens on aging populations. The pathogenesis of PD is complex and multifaceted. Emerging evidence highlights microRNA (miRNA) dysregulation as a critical regulatory layer that drives PD progression. These small noncoding RNAs mediate posttranscriptional gene regulation through target mRNA binding, inducing either transcript degradation or translational repression. This article reviews the distinct miRNAs that orchestrate PD pathogenesis by disrupting mitochondrial homeostasis, lysosomal clearance pathways, ferroptosis regulation, and neuroinflammatory responses. Notably, some miRNAs achieve these effects by selectively targeting risk genes central to PD pathology. Crucially, certain miRNAs exhibit aberrant expression patterns in the brain tissues and biofluids of PD patients or models, highlighting their potential as minimally invasive diagnostic or prognostic biomarkers. Furthermore, this review highlights the novel role of exosomes as miRNA carriers, offering innovative possibilities for PD therapeutic interventions. With the deepening understanding of miRNA research advances in PD, we propose that these insights may not only inform PD treatment strategies but also hold relevance for addressing other genetic disorders.