Cross-link Between CircRNAs and Neuroinflammation in Parkinson's Disease

Parkinson's disease (PD) is a major neurodegenerative disorder affecting a large number of people worldwide. PD has been characterized by motor abnormalities, as well as non-motor abnormalities that lower patients' quality of life. The pathological features of PD include the substantia nigra's dopaminergic neurons degradation, leading to a progressive clinical course, Lewy bodies and Lewy neurites, which are primarily composed of α-synuclein, and chronic neuroinflammatory changes that contribute to disease progression. Circular RNAs (circRNAs) are a type of circular single-stranded RNAs possessing high stability. Their expression varies depending on tissue type, cell type, and developmental stage, suggesting their roles in regulating biological processes. Recent research has indicated that circRNAs participate in PD pathophysiology by modulating neuroinflammation, immune response, mitochondrial dysfunction, and reactive oxygen species accumulation. Mechanistically, many circRNAs appear to act as molecular sponges for microRNAs, thereby influencing the expression of key genes involved in inflammatory signaling, synaptic regulation, and neuronal survival. This review summarizes the impact of circRNAs on neuroinflammation, astrocyte/microglia dysfunction, mitochondrial damage, and oxidative stress in PD. It also summarizes experimental evidence from cellular and animal models showing that multiple circRNAs can modulate inflammatory pathways in PD and related neurological disorders. However, only a limited number of studies have evaluated circRNAs as biomarkers or therapeutic targets in patient samples, and comprehensive in vivo validation of circRNA-miRNA-target network remains insufficient. A better understanding of these regulatory pathways may help identify clinically relevant biomarkers and support the development of circRNA-based therapeutic strategies for PD.