Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interaction
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223018643 |
| _version_ | 1827781721496485888 |
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| author | Zhidan Liu Kang Kang Shulin Shan Shuai Wang Xianjie Li Hui Yong Zhengcheng Huang Yiyu Yang Zhaoxiong Liu Yanan Sun Yao Bai Fuyong Song |
| author_facet | Zhidan Liu Kang Kang Shulin Shan Shuai Wang Xianjie Li Hui Yong Zhengcheng Huang Yiyu Yang Zhaoxiong Liu Yanan Sun Yao Bai Fuyong Song |
| author_sort | Zhidan Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T15:22:47Z |
| format | Article |
| id | doaj.art-0bad7bbc4e504675a0dd3df3d02e9b68 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:22:47Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-0bad7bbc4e504675a0dd3df3d02e9b682023-10-28T05:08:27ZengElsevieriScience2589-00422023-10-012610107787Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interactionZhidan Liu0Kang Kang1Shulin Shan2Shuai Wang3Xianjie Li4Hui Yong5Zhengcheng Huang6Yiyu Yang7Zhaoxiong Liu8Yanan Sun9Yao Bai10Fuyong Song11Department of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, ChinaQingdao Municipal Center for Disease Control & Prevention, Qingdao, Shandong 266033, ChinaDepartment of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, ChinaDepartment of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, ChinaInstitute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, Guangdong 510075, ChinaQingdao Municipal Center for Disease Control & Prevention, Qingdao, Shandong 266033, ChinaDepartment of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, ChinaDepartment of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, ChinaDepartment of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, ChinaDepartment of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing 100021, ChinaNHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing 100021, China; Corresponding authorDepartment of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223018643Biological sciencesBiochemistryNeuroscienceCell biology |
| spellingShingle | Zhidan Liu Kang Kang Shulin Shan Shuai Wang Xianjie Li Hui Yong Zhengcheng Huang Yiyu Yang Zhaoxiong Liu Yanan Sun Yao Bai Fuyong Song Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interaction iScience Biological sciences Biochemistry Neuroscience Cell biology |
| title | Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interaction |
| title_full | Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interaction |
| title_fullStr | Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interaction |
| title_full_unstemmed | Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interaction |
| title_short | Chronic carbon disulfide exposure induces parkinsonian pathology via α-synuclein aggregation and necrosome complex interaction |
| title_sort | chronic carbon disulfide exposure induces parkinsonian pathology via α synuclein aggregation and necrosome complex interaction |
| topic | Biological sciences Biochemistry Neuroscience Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223018643 |
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