代森锰暴露诱导神经毒性和α-突触核蛋白聚集的机制

章智冰; 方艳艳; 彭锟; 高翔; 刘泽华; 李飞; 刘朝阳

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中国环境科学 ›› 2026, Vol. 46 ›› Issue (1) : 493-502.

环境毒理与健康

代森锰暴露诱导神经毒性和α-突触核蛋白聚集的机制

章智冰¹, 方艳艳¹, 彭锟¹, 高翔¹, 刘泽华², 李飞¹, 刘朝阳^1,3

作者信息 +

Mechanisms of Maneb exposure-induced neurotoxicity and α-Synuclein aggregation

ZHANG Zhi-bing¹, FANG Yan-yan¹, PENG Kun¹, GAO Xiang¹, LIU Ze-hua², LI Fei¹, LIU Chao-yang^1,3

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文章历史 +

摘要

以HEK293-α-syn细胞和野生型小鼠原代皮质神经元为实验模型,深入探讨了不同浓度(0,0.1,1.0,5.0mg/L)Maneb暴露的环境神经毒性及机制.结果表明,Maneb暴露浓度依赖性地抑制HEK293-α-syn细胞活性,诱导原代神经元损伤.Maneb暴露浓度越高,其毒性作用越显著,其中0.1mg/L实验组中神经元凋亡率接近60%.此外,Maneb暴露诱导HEK293-α-syn细胞和原代神经元内α-syn发生聚集,刺激其在S129位点发生异常磷酸化,不溶性磷酸化α-syn水平上调,进一步形成路易小体(LB)样聚集体,表明Maneb对帕金森(PD)样神经毒性的诱发作用.

Abstract

HEK293-α-syn cells and primary cortical neurons of wild-type mice were used as experimental models to deeply explore the environmental neurotoxicity and mechanism of Maneb exposure at different concentrations (0, 0.1, 1.0, 5.0mg/L). The results showed that Maneb exposure inhibited the activity of HEK293-α-syn cells in a dose-dependent manner and induced primary neuronal damage. The higher the Maneb exposure concentration, the more significant its toxic effect. In the 0.1mg/L experimental group, the apoptosis rate of neurons was close to 60%. In addition, Maneb exposure induced the aggregation of α-syn in HEK293-α-syn cells and primary neurons, stimulated its abnormal phosphorylation at the S129 site, and upregulated the level of insoluble phosphorylated α-syn, further forming Lewy body (LB)-like aggregates, indicating that Maneb induces Parkinson's (PD)-like neurotoxicity.

导出引用

章智冰, 方艳艳, 彭锟, 高翔, 刘泽华, 李飞, 刘朝阳. 代森锰暴露诱导神经毒性和α-突触核蛋白聚集的机制[J]. 中国环境科学. 2026, 46(1): 493-502

ZHANG Zhi-bing, FANG Yan-yan, PENG Kun, GAO Xiang, LIU Ze-hua, LI Fei, LIU Chao-yang. Mechanisms of Maneb exposure-induced neurotoxicity and α-Synuclein aggregation[J]. China Environmental Science. 2026, 46(1): 493-502

中图分类号： X503.1

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