Parkinson’s disease (PD) is the second most common neurodegenerative disease; it mainly occurs in the elderly population. Cuproptosis is a newly discovered form of regulated cell death involved in the progression of various diseases. Combining multiple GEO datasets, we analyzed the expression profile and immunity of cuproptosis-related genes (CRGs) in PD. Dysregulated CRGs and differential immune responses were identified between PD and non-PD substantia nigra. Two CRG clusters were defined in PD. Immune analysis suggested that CRG cluster 1 was characterized by a high immune response. The enrichment analysis showed that CRG cluster 1 was significantly enriched in immune activation pathways, such as the Notch pathway and the JAK-STAT pathway. KIAA0319, AGTR1, and SLC18A2 were selected as core genes based on the LASSO analysis. We built a nomogram that can predict the occurrence of PD based on the core genes. Further analysis found that the core genes were significantly correlated with tyrosine hydroxylase activity. This study systematically evaluated the relationship between cuproptosis and PD and established a predictive model for assessing the risk of cuproptosis subtypes and the outcome of PD patients. This study provides a new understanding of PD-related molecular mechanisms and provides new insights into the treatment of PD.

Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson’s disease (PD), and a noble cause of disability in advanced PD patients. Circular RNA (circRNA) is a novel type of non-coding RNA with a covalently closed-loop structure, which can regulate gene expression and participate in many biological processes. However, the biological roles of circRNAs in LID are not completely known. In the present study, we established typical LID rat models by unilateral lesions of the medial forebrain bundle and repeated levodopa therapy. High-throughput next-generation sequencing was used to screen circRNAs differentially expressed in the brain of LID and non-LID (NLID) rats, and key circRNAs were selected according to bioinformatics analyses. Regarding fold change ≥2 and p < 0.05 as the cutoff value, there were a total of 99 differential circRNAs, including 39 up-regulated and 60 down-regulated circRNAs between the NLID and LID groups. The expression of rno-Rsf1_0012 was significantly increased in the striatum of LID rats and competitively bound rno-mir-298-5p. The high expression of target genes PCP and TBP in LID rats also supports the conclusion that rno-Rsf1_0012 may be related to the occurrence of LID.