School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Trends Mol Med. 2022 Jul;28(7):555-568. doi: 10.1016/j.molmed.2022.04.011. Epub 2022 May 22.
Metals are ubiquitous chemical entities involved in a myriad of biological processes. Despite their integral role in sustaining life, overexposure can lead to deleterious neurological outcomes posing a public health concern. Excess exposure to metals has been associated with aberrant neurodevelopmental and neurodegenerative diseases and prominently contributes to environmental risk for neurological disorders. Here, we use manganese (Mn) to exemplify the gap in our understanding of the mechanisms behind acute metal toxicity and their relationship to chronic toxicity and disease. This challenge frustrates understanding of how individual exposure histories translate into preventing and treating brain diseases from childhood through old age. We discuss ways to enhance the predictive value of preclinical models and define mechanisms of chronic, persistent, and latent neurotoxicity.
金属是无处不在的化学实体，参与了无数的生物过程。尽管它们在维持生命方面起着不可或缺的作用，但过度暴露会导致有害的神经后果，引起公共卫生关注。过多接触金属与神经发育和神经退行性疾病的异常有关，并显著增加了神经紊乱的环境风险。在这里，我们使用锰 (Mn) 来举例说明我们对急性金属毒性背后的机制及其与慢性毒性和疾病关系的理解存在差距。这一挑战阻碍了我们理解个体暴露史如何转化为预防和治疗从儿童期到老年期的脑部疾病。我们讨论了增强临床前模型的预测价值和定义慢性、持续和潜伏神经毒性机制的方法。
