2. Academic Validation
  3. Lead exposure induces neurodysfunction through caspase-1-mediated neuronal pyroptosis

Lead exposure induces neurodysfunction through caspase-1-mediated neuronal pyroptosis

  • Environ Res. 2024 Aug 15:255:119210. doi: 10.1016/j.envres.2024.119210.
Dongjie Peng 1,  Leilei Wang 1,  Yuanyuan Fang 1,  Lili Lu 1,  Zhaocong Li 1,  Siyang Jiang 1,  Jing Chen 1,  Michael Aschner 2,  Shaojun Li 3,  Yueming Jiang 4
Affiliations

Affiliations

  • 1 Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China.
  • 2 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • 3 Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. Electronic address: lishaojun0613@163.com.
  • 4 Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. Electronic address: ymjiang@sr.gxmu.edu.cn.
PMID: 38795947 DOI: 10.1016/j.envres.2024.119210
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.

Keywords

Lead; Neurodysfunction; Neuroinflammation; Pyroptosis; Sodium para-aminosalicylic acid.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z