Niloufar Rezaei, Maryam Zivari, Mansure Kazemi, Behrang Alani, Mahdi Noureddini, Mahdi Rafiyan, Ashkan Bahrami, Mohammad Sepehr Yazdani, Reza Eshraghi, Tahereh Mazoochi, Hamed Mirzaei
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of α-synuclein. Non-coding RNAs (ncRNAs)-including microRNAs, long non-coding RNAs, and circular RNAs-have emerged as critical regulators in PD pathogenesis by modulating pathways such as neuroinflammation, mitochondrial function, and protein clearance. Furthermore, exosomal ncRNAs facilitate intercellular communication, propagating pathological signals but also offering therapeutic potential. This review synthesizes the current understanding of ncRNA involvement in PD, structuring the analysis around key pathogenic mechanisms. We provide a critical perspective on the strengths and weaknesses of the current evidence, evaluate the major challenges facing the field-including biomarker validation and therapeutic delivery-and propose a path forward for future research. A deeper, more integrated understanding of these ncRNA networks is essential for developing novel diagnostics and treatments to halt the progression of PD.