School of Health Sciences, Purdue University, West Lafayette, IN 47907-2051, United States.
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
Biochim Biophys Acta Gen Subj. 2019 Dec;1863(12):129300. doi: 10.1016/j.bbagen.2019.02.002. Epub 2019 Feb 10.
Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS) with apparent indiscriminate disruption of multiple homeostatic pathways. However, genetic and environmental modifiers contribute significant variability to neurotoxicity associated with human exposures. MeHg displays developmental stage and neural lineage selective neurotoxicity. To identify mechanistic-based neuroprotective strategies to mitigate human MeHg exposure risk, it will be critical to improve our understanding of the basis of MeHg neurotoxicity and of this selective neurotoxicity. Here, we propose that human-based pluripotent stem cell cellular approaches may enable mechanistic insight into genetic pathways that modify sensitivity of specific neural lineages to MeHg-induced neurotoxicity. Such studies are crucial for the development of novel disease modifying strategies impinging on MeHg exposure vulnerability.
甲基汞（MeHg）是一种强效的神经毒素，可影响发育中和成熟中的中枢神经系统（CNS），明显破坏多种体内平衡途径。然而，遗传和环境修饰因子对与人类暴露相关的神经毒性有很大的可变性。MeHg 表现出发育阶段和神经谱系选择性神经毒性。为了确定基于机制的神经保护策略来减轻人类 MeHg 暴露风险，提高我们对 MeHg 神经毒性和这种选择性神经毒性基础的理解将是至关重要的。在这里，我们提出，基于人类的多能干细胞细胞方法可以使我们深入了解改变特定神经谱系对 MeHg 诱导的神经毒性敏感性的遗传途径的机制。这些研究对于开发新型疾病修饰策略以影响 MeHg 暴露的脆弱性至关重要。
