Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interaction

Autor: Zhidan Liu, Kang Kang, Shulin Shan, Shuai Wang, Xianjie Li, Hui Yong, Zhengcheng Huang, Yiyu Yang, Zhaoxiong Liu, Yanan Sun, Yao Bai, Fuyong Song
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: iScience, Vol 26, Iss 10, Pp 107787- (2023)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2023.107787
Popis: Summary: Exposure to carbon disulfide (CS2) has been associated with an increased incidence of parkinsonism in workers, but the mechanism underlying this association remains unclear. Using a rat model, we investigated the effects of chronic CS2 exposure on parkinsonian pathology. Our results showed that CS2 exposure leads to significant motor impairment and neuronal damage, including loss of dopaminergic neurons and degeneration of the substantia nigra pars compacta (SNpc). The immunoassays revealed that exposure to CS2 induces aggregation of α-synuclein and phosphorylated α-synuclein, as well as activation of necroptosis in the SNpc. Furthermore, in vitro and in vivo experiments demonstrated that the interaction between α-synuclein and the necrosome complex (RIP1, RIP3, and MLKL) is responsible for the loss of neuronal cells after CS2 exposure. Taken together, our results demonstrate that CS2-mediated α-synuclein aggregation can induce dopaminergic neuron damage and parkinsonian behavior through interaction with the necrosome complex.
Databáze: Directory of Open Access Journals