机构：[1]The First Affiliated Hospital of Jinan University, Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of the Chinese Ministry of Education, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, and The Sixth Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China[2]Shanghai Institute for Biomedical and Pharmaceutical Technologies, National Health Commission Key Laboratory of Reproduction Regulation, Shanghai, China[3]School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, China[4]Key Laboratory of CNS Regeneration, Ministry of Education, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China[5]State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the gradual loss of midbrain dopaminergic neurons in association with aggregation of α-synuclein. Oxidative damage has been widely implicated in this disease, though the mechanisms involved remain elusive. Here, we demonstrated that preferential accumulation of peroxidized phospholipids and loss of the antioxidant enzyme glutathione peroxidase 4 (GPX4) were responsible for vulnerability of midbrain dopaminergic neurons and progressive motor dysfunctions in a mouse model of PD. We also established a mechanism wherein iron-induced dopamine oxidation modified GPX4, thereby rendering it amenable to degradation via the ubiquitin-proteasome pathway. In conclusion, this study unraveled what we believe to be a novel pathway for dopaminergic neuron degeneration during PD pathogenesis, driven by dopamine-induced loss of antioxidant GPX4 activity.
基金：
This work was supported, in
part, by Natural Science Foundation of China (82125038, 82274123,
82274403, 81873209, 81903821, and 81973718), the Local Innovative
and Research Teams Project of Guangdong Pearl River Talents
Program (2017BT01Y036), and GDUPS (2019), Natural Science
Foundation of Guangdong (2021A1515011297), Science and Technology
Program of Guangzhou (201903010062, 907158833068),
and the Innovation Team Project of Guangdong Provincial Department
of Education (2020KCXTD003).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|1 区医学
小类|1 区医学：研究与实验
最新[2025]版：
大类|1 区医学
小类|1 区医学：研究与实验
第一作者：
第一作者机构：[1]The First Affiliated Hospital of Jinan University, Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of the Chinese Ministry of Education, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, and The Sixth Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
共同第一作者：
通讯作者：
通讯机构：[1]The First Affiliated Hospital of Jinan University, Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of the Chinese Ministry of Education, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, and The Sixth Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China[3]School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, China[4]Key Laboratory of CNS Regeneration, Ministry of Education, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China[5]State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.[*1]Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China
推荐引用方式(GB/T 7714)：
Sun Jie,Lin Xiao-Min,Lu Dan-Hua,et al.Midbrain dopamine oxidation links ubiquitination of glutathione peroxidase 4 to ferroptosis of dopaminergic neurons[J].The Journal of clinical investigation.2023,133(10):doi:10.1172/JCI165228.
APA：
Sun Jie,Lin Xiao-Min,Lu Dan-Hua,Wang Meng,Li Kun...&He Rong-Rong.(2023).Midbrain dopamine oxidation links ubiquitination of glutathione peroxidase 4 to ferroptosis of dopaminergic neurons.The Journal of clinical investigation,133,(10)
MLA：
Sun Jie,et al."Midbrain dopamine oxidation links ubiquitination of glutathione peroxidase 4 to ferroptosis of dopaminergic neurons".The Journal of clinical investigation 133..10(2023)
医学