PARP1 promotes NLRP3 activation via blocking TFEB-mediated autophagy in rotenone-induced neurodegeneration

He Zhang; Zhefan Xie; Yongming Peng; Ailun Xie; Chunlai Fu; Dongyan Zheng; ZiWei Cai; Jiahong Zhong; Qiang Ming; Mingque Li; Renjian Lu; Xin Liu; Jialong Chen

Ecotoxicology and Environmental Safety (Mar 2023)

PARP1 promotes NLRP3 activation via blocking TFEB-mediated autophagy in rotenone-induced neurodegeneration

He Zhang,
Zhefan Xie,
Yongming Peng,
Ailun Xie,
Chunlai Fu,
Dongyan Zheng,
ZiWei Cai,
Jiahong Zhong,
Qiang Ming,
Mingque Li,
Renjian Lu,
Xin Liu,
Jialong Chen

Affiliations

He Zhang: Department of Preventive Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Correspondence to: Department of Environmental and Occupational Health, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China.
Zhefan Xie: Department of Emergency Intensive Care Unit, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan, Guangdong, PR China
Yongming Peng: Department of Preventive Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China
Ailun Xie: Department of Preventive Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China
Chunlai Fu: Department of Emergency Intensive Care Unit, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan, Guangdong, PR China
Dongyan Zheng: Department of Preventive Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China
ZiWei Cai: Department of Preventive Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China
Jiahong Zhong: Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 528400, PR China
Qiang Ming: Department of Neurology, Longgang Central Hospital of Shenzhen, 518116, PR China
Mingque Li: Department of Preventive Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China
Renjian Lu: Department of Preventive Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China
Xin Liu: Department of Preventive Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Correspondence to: Department of Environmental and Occupational Health, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China.
Jialong Chen: Department of Preventive Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China; Correspondence to: Department of Environmental and Occupational Health, School of Public Health, Guangdong Medical University, Dongguan 523808, PR China.

Journal volume & issue: Vol. 252
p. 114630

Abstract

Read online

Rotenone, a widely used pesticide, causes dopaminergic neurons loss and increase the risk of Parkinson's disease (PD). However, few studies link the role of PARP1 to neuroinflammatory response and autophagy dysfunction in rotenone-induced neurodegeneration. Here, we identified that PARP1 overactivation caused by rotenone led to autophagy dysfunction and NLRP3-mediated inflammation. Further results showed that PARP1 inhibition could reduce NLRP3-mediated inflammation, which was effectively eliminated by TFEB knockdown. Moreover, PARP1 poly(ADP-ribosyl)ated TFEB that reduced autophagy. Of note, PARP1 inhibition could rescue rotenone-induced dopaminergic neurons loss. Overall, our study revealed that PARP1 blocks autophagy through poly (ADP-ribosyl)ating TFEB and inhibited NLRP3 degradation, which suggests that intervention of PARP1-TFEB-NLRP3 signaling can be a new treatment strategy for rotenone-induced neurodegeneration.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

About the journal

Abstract

Keywords