Abstract
We aimed to explore the mechanism of pramipexole (PPX) actions in the treatment of Parkinson’s disease (PD). Genes related to PD and PPX were screened through bioinformatics retrieval. The PD model was constructed by applying 1-methyl-4-phenylpyridinium (MMP+). The RNA expression levels of circSNCA, SNCA, apoptosis-related genes (BCL2, CASP3, BAX, PTEN and P53) and miR-7 were detected by qRT-PCR. Protein expression was determined by western blot. The interactions between circSNCA-miR-7-SNCA were verified by dual luciferase assay and immunofluorescence localization. Cell viability was determined by MTT assay. SNCA and circSNCA expression levels in PD were downregulated after PPX treatment, consistent with the levels of pro-apoptotic genes. CircSNCA increased SNCA expression by downregulating miR-7 in PD as a competitive endogenous RNA (ceRNA). Lower circSNCA expression was associated with the reduced expression of pro-apoptotic (CASP3, BAX, PTEN and P53) proteins. CircSNCA downregulation could decrease apoptosis and induce autophagy in PD. In conclusion, the downregulation of circSNCA by PPX treatment reduced cell apoptosis and promoted cell autophagy in PD via a mechanism that served as a miR-7 sponge to upregulate SNCA.
Highlights
Parkinson’s disease (PD) is a progressive neurodegenerative disease that usually presents in people during old or late middle age with noticeable outward symptoms generally appearing in a person’s sixties
We first identified the significantly reduced expression of SNCA and circSNCA after PPX treatment
We investigated the endogenous competition between circSNCA and SNCA mRNA and found that circSNCA was a competitive endogenous RNA (ceRNA) of miR-7 in PD, binding with miR-7 and upregulating its target gene, SNCA
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disease that usually presents in people during old or late middle age with noticeable outward symptoms generally appearing in a person’s sixties. The phenotypes of this disorder include progressive deterioration of autonomic and motor functions, with cognitive decline in most cases. PDX can be advantageously administered as a monotherapy or an adjunctive therapy to levodopa to decrease side effects and increase effectiveness in both early and advanced PD treatments [3] These results were the basis for considering whether there were other mechanisms involved in PPX treatment of PD by regulating gene expression
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