The miR-650/GCLM Axis Is Associated With Oxidative Stress and Neuroinflammation in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is one of the common neurodegenerative diseases and is difficult to cure. The mechanisms underlying PD are incompletely understood. OBJECTIVE: This study investigated the changes in miR-650 expression in PD patients, aiming to assess its potential diagnostic value, and preliminarily explored the molecular mechanism by which miR-650 regulates oxidative damage and neuroinflammation. METHODS: The clinical data and blood samples were collected from PD patients. PD models were established in MPTP-treated mice and MPP+-treated BV2 cells. The function and molecular mechanism of miR-650 were then investigated through behavioral assessments, data analysis (such as ROC analysis and logistic regression analysis), and molecular analysis (such as Western blot, ELISA, and flow cytometry). RESULTS: miR-650 was upregulated in PD and exhibited diagnostic potential. The MPTP-induced PD mouse model displayed motor dysfunction, increased accumulation of α-synuclein, enhanced oxidative stress and inflammatory response. These symptoms were effectively alleviated by inhibiting miR-650. In BV2 cells, inhibiting miR-650 reduced oxidative stress and inflammatory responses by negatively regulating GCLM. CONCLUSION: The upregulated expression of miR-650 may have potential diagnostic value in PD. Animal and cellular experiments indicate that inhibiting miR-650 alleviates the motor disorders, oxidative stress, and inflammatory responses in PD by negatively regulating GCLM.