Expanding Therapeutic Horizons in Parkinson's Disease Through MicroRNA-Based Interventions: A Comprehensive Review

Parkinson's disease (PD) is a neurodegenerative disorder with rapidly increasing prevalence, characterized by dopaminergic neuronal loss and α-synuclein aggregation. Current therapies provide only symptomatic benefit and do not alter the disease course. MicroRNAs (miRNAs), small noncoding RNAs that regulate gene expression, are increasingly recognized as key modulators of PD pathogenesis, influencing oxidative stress, mitochondrial dysfunction, neuroinflammation, and proteostasis. Therapeutic modulation of miRNAs in PD has centered on two complementary approaches: miRNA inhibitors (antagomiRs), which silence pathogenic miRNAs, and miRNA mimics (agomiRs), which restore the activity of protective ones. This review integrates current insights into miRNA dysregulation in PD and evaluates the hurdles limiting therapeutic translation. Specific miRNAs such as miR-7, miR-153, and miR-34b/c directly regulate SNCA expression, whereas others influence clearance pathways and stress responses. Although miRNA-based therapeutics offer considerable promise, their clinical utility remains constrained by challenges of delivery, specificity, and standardization. This review highlights strategies to harness miRNA modulation as a targeted therapeutic avenue in PD.