| 研究実績の概要 |
Oxidative stress plays an important role in the degeneration of neurons and considered to be one of the main toxic factors caused by accumulated protein oligomers, an iconic feature in many neurodegenerative diseases including Alzheimer's and Parkinson's disease. Increased reactive oxygen species (ROS) production or disruptions in the physiologic maintenance of the redox potential in neurons interfere with several biological processes, ultimately leading to cell death. In this study, we found that the ubiquitin-specific protease 10 (USP10) protein reduces dopamine-induced ROS production of neuronal cells and ROS-dependent apoptosis by stimulating the antioxidant activity of Nrf2. USP10 interacted with the Nrf2 activator p62, increased the phosphorylation of p62, increased the interaction of p62 with the Nrf2 inhibitor Keap1, and stimulated Nrf2 antioxidant transcriptional activity. In addition, USP10 augmented dopamine-induced Nrf2 translation. Together, our results indicate that USP10 is a key regulator of Nrf2 antioxidant activity in neuronal cells and suggest that USP10 activators are promising therapeutic agents for oxidative stress-related diseases, including Alzheimer's and Parkinson's diseases.
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