| 论文题目: | GSNOR Deficiency Attenuates MPTP-induced Neurotoxicity and Autophagy by Facilitating CDK5 S-nitrosation in a Mouse Model of Parkinson's Disease |
| 作者: | Jiao, LJ; Su, LY; Liu, QJ ; Luo, RC; Qiao, XH ; Xie, T; Yang, LX ; Chen, C; Yao, YG |
| 联系作者: | yaoyg@mail.kiz.ac.cn |
| 发表年度: | 2022 |
| DOI: | DOI10.1016/j.freeradbiomed.2022.07.016 |
| 摘要: | The S-nitrosoglutathione reductase (GSNOR) is a key denitrosating enzyme that regulates protein S-nitrosation, a process which has been found to be involved in the pathogenesis of Parkinson's disease (PD). However, the physiological function of GSNOR in PD remains unknown. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, we found that GSNOR expression was significantly increased and accompanied by autophagy mediated by MPTP-induced cyclin dependent kinase 5 (CDK5), behavioral dyskinesias and dopaminergic neuron loss. Whereas, knockout of GSNOR, or treatment with the GSNOR inhibitor N6022, alleviated MPTP-induced PD-like pathology and neurotoxicity. Mechanistically, deficiency of GSNOR inhibited MPTP-induced CDK5 kinase activity and CDK5-mediated autophagy by increasing S-nitrosation of CDK5 at Cys83. Our study indicated that GSNOR is a key regulator of CDK5 S-nitrosation and is actively involved in CDK5-mediated autophagy induced by MPTP |
| 刊物名称: | Free Radical Biology and Medicine |
| 论文出处: | https://www.sciencedirect.com/science/article/pii/S0891584922004993?via%3Dihub |
| 影响因子: | 8.101(2021IF) |
