Chronic Carbon Disulfide Exposure Induces Parkinsonian Pathology Via α-synuclein Aggregation and Necrosome Complex Interaction

Overview

Journal iScience

Publisher Cell Press

Date 2023 Sep 21

PMID 37731606

Authors

Zhidan Liu

Kang Kang

Shulin Shan

Shuai Wang

Xianjie Li

Hui Yong

Zhengcheng Huang

Yiyu Yang

Zhaoxiong Liu

Yanan Sun

Yao Bai

Fuyong Song

Affiliations

Soon will be listed here.

Abstract

Exposure to carbon disulfide (CS) 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 CS exposure on parkinsonian pathology. Our results showed that CS 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 CS induces aggregation of α-synuclein and phosphorylated α-synuclein, as well as activation of necroptosis in the SNpc. Furthermore, and 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 CS exposure. Taken together, our results demonstrate that CS-mediated α-synuclein aggregation can induce dopaminergic neuron damage and parkinsonian behavior through interaction with the necrosome complex.

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PMID: 40075434 PMC: 11899656. DOI: 10.1186/s12995-025-00454-9.

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