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

ABSTRACT: 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.

SUBMITTER: Liu Z

PROVIDER: S-EPMC10507234 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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

Liu Zhidan Z Kang Kang K Shan Shulin S Wang Shuai S Li Xianjie X Yong Hui H Huang Zhengcheng Z Yang Yiyu Y Liu Zhaoxiong Z Sun Yanan Y Bai Yao Y Song Fuyong F

iScience 20230830 10

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 ...[more]

PMID: 37731606

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Dataset Information

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

Publications

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

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