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PARP1 promotes NLRP3 activation via blocking TFEB-mediated autophagy in rotenone-induced neurodegeneration.
- Source :
-
Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2023 Mar 01; Vol. 252, pp. 114630. Date of Electronic Publication: 2023 Feb 08. - Publication Year :
- 2023
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Abstract
- 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.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
NLR Family, Pyrin Domain-Containing 3 Protein genetics
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Autophagy
Inflammation
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors pharmacology
Poly (ADP-Ribose) Polymerase-1 genetics
Rotenone toxicity
Parkinson Disease genetics
Parkinson Disease metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2414
- Volume :
- 252
- Database :
- MEDLINE
- Journal :
- Ecotoxicology and environmental safety
- Publication Type :
- Academic Journal
- Accession number :
- 36764072
- Full Text :
- https://doi.org/10.1016/j.ecoenv.2023.114630