Nrf2 Inhibits the Progression of Parkinson’s Disease by Upregulating AABR07032261.5 to Repress Pyroptosis

OBJECTIVE: Parkinson’s disease (PD) is associated with dysregulated neural cell death, such as pyroptosis, but its regulatory mechanisms are poorly understood. This study investigated roles of nuclear factor E2-related factor 2 (Nrf2) in regulating pyroptosis and PD development. METHODS: Cellular and rat PD models established by 6-OHDA exposure were subjected to Nrf2 overexpression. Neurobehavioral functions were assessed by the traction test, Morris Water Maze, and open field test. Cell proliferation was analyzed by MTS assay, while flow cytometry was applied to quantify levels of reactive oxygen species (ROS) and apoptosis. Nissl bodies in rat brains were detected by Nissl staining, and cell apoptosis in brain tissues was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Differential expression of lncRNA and mRNA was characterized by deep sequencing. RESULTS: A cellular PD model was successfully established by inducing PC12 cell differentiation with nerve growth factor-β and exposing differentiated cells to 6-OHDA. Cells exhibited significantly increased ROS levels, enhanced pyroptosis, and inhibited Nrf2 phosphorylation. The rat PD model exhibited impaired muscle strength, increased pyroptosis, and repressed Nrf2 phosphorylation. Nrf2 overexpression effectively repressed pyroptosis in both cellular and rat PD models. Marked alterations of lncRNA and mRNA profiles were induced by Nrf2 overexpression in the cellular PD model, which involved multiple signaling pathways. Silencing of the lncRNA AABR07032261.5 significantly promoted pyroptosis in the cellular PD model. CONCLUSION: Nrf2 suppressed PD pathogenesis in cellular and animal models by promoting AABR07032261.5, which repressed pyroptosis.