金属锰暴露致神经毒性的多组学研究进展

Multiomics Research Progress on Neurotoxicity Induced by Manganese Metal Exposure

锰是环境重金属污染物之一,长期暴露于金属锰或其无机化合物主要引发锰中毒或亚临床神经功能缺陷。锰暴露诱导的神经毒性对遗传易感性、基因表达调控、代谢稳态的影响机制复杂,涉及多靶点,然而常规机制研究往往只能局限于单一通路。鉴于工作场所和环境中重金属锰的分布日益广泛,需要更明确地界定锰的神经毒性作用网络,实现多靶点预防和治疗。多组学技术及其相关分析可在不同的功能水平上对疾病发生发展进程中的差异化进行描述。综述了基因组学、表观遗传学、转录组学、代谢组学在金属锰暴露致神经毒性中的研究结果,探讨潜在的代表性生物标志物,支持多组学方法的整合应用,构建锰的神经毒性作用网络,并对未来研究方向提出展望。

Manganese is one of the heavy metal pollutants in environment.Long-term exposure to metallic manganese or its inorganic compounds can lead to manganese poisoning or subclinical neurological deficits.The mechanism of neurotoxicity induced by manganese exposure on genetic susceptibility,gene expression regulation,and metabolic homeostasis is complex and involves multiple targets.However,conventional mechanism research is often limited to a single pathway.Given the increasingly distribution of manganese in the workplace and daily environment,it is necessary to more clearly define the neurotoxic network of manganese and achieve multi-target prevention and remedy.Multi-omics technique and its correlation analysis can elaborate the differentiation in the process of disease at multiple dimensions.In this review,the research results of genomics,epigenetics,transcriptomics,and metabolomics in the neurotoxicity of manganese exposure were summarized,potential representative biomarkers were explored,the integration and application of multi-omics methods to construct a network of manganese neurotoxicity effects were supported,and prospects for future research directions were proposed.