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Lead exposure induces neurodysfunction through caspase-1-mediated neuronal pyroptosis.
- Source :
-
Environmental Research . Aug2024, Vol. 255, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
-
Abstract
- Chronic lead (Pb) exposure causes neurodysfunction and contributes to the development of neurodegenerative disease. However, the mechanism of Pb-induced neurological dysfunction have yet to be fully elucidated. This study determined the role pyroptosis plays in Pb-induced neurodysfunction in neurons. We used both in vitro and in vivo approaches to explore whether Pb exposure induces caspase-1-mediated pyroptosis in neurons and its relationship to Pb-induced neurological disorders. Our findings showed that caspase-1-mediated pyroptosis in Pb-exposed neurons activated glycogen synthase kinase 3 protease activity by disrupting Ca2+/calmodulin-dependent protein kinase II/cAMP-response element binding protein pathway, leading to neurological disorders. Moreover, the caspase-1 inhibition VX-765 or the non-steroidal anti-inflammatory drug sodium para-aminosalicylic acid (PAS-Na) attenuated the Pb-induced neurological disorders by alleviating caspase-1 mediated neuronal pyroptosis. Our novel studies suggest that caspase-1-mediated pyroptosis in neurons represents a potential mechanism for Pb-induced neurodysfunction, identifying a putative target for attenuating the neurodegenerative effects induced by this metal. [Display omitted] • Pb induces pyroptosis in neurons. • Caspase-1 mediates neuronal pyroptosis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00139351
- Volume :
- 255
- Database :
- Academic Search Index
- Journal :
- Environmental Research
- Publication Type :
- Academic Journal
- Accession number :
- 177756942
- Full Text :
- https://doi.org/10.1016/j.envres.2024.119210