Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Ecotoxicology and environmental safety, 2023-03, Vol.252, p.114630-114630, Article 114630

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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. [Display omitted] •The role of PARP1 to neuroinflammatory response and autophagy dysfunction was identified in rotenone-induced neurodegeneration.•PARP1 blocks autophagy through poly (ADP-ribosyl)ating TFEB and inhibited NLRP3 degradation.•PARP1-TFEB-NLRP3 signaling can be a new treatment strategy for rotenone-induced neurodegeneration.