Liu Zhidan, Kang Kang, Shan Shulin, Wang Shuai, Li Xianjie, Yong Hui, Huang Zhengcheng, Yang Yiyu, Liu Zhaoxiong, Sun Yanan, Bai Yao, Song Fuyong
Department of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Qingdao Municipal Center for Disease Control & Prevention, Qingdao, Shandong 266033, China.
iScience. 2023 Aug 30;26(10):107787. doi: 10.1016/j.isci.2023.107787. eCollection 2023 Oct 20.
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.
接触二硫化碳（CS）与工人帕金森症发病率增加有关，但这种关联背后的机制仍不清楚。我们使用大鼠模型研究了慢性CS暴露对帕金森病病理的影响。我们的结果表明，CS暴露会导致明显的运动障碍和神经元损伤，包括多巴胺能神经元丧失和黑质致密部（SNpc）变性。免疫分析显示，CS暴露会诱导α-突触核蛋白和磷酸化α-突触核蛋白聚集，以及SNpc中的坏死性凋亡激活。此外，实验表明，α-突触核蛋白与坏死小体复合物（RIP1、RIP3和MLKL）之间的相互作用是CS暴露后神经元细胞丧失的原因。综上所述，我们的结果表明，CS介导的α-突触核蛋白聚集可通过与坏死小体复合物相互作用诱导多巴胺能神经元损伤和帕金森样行为。
