Farina Marcelo, Aschner Michael
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
Adv Neurobiol. 2017;18:267-286. doi: 10.1007/978-3-319-60189-2_13.
Methylmercury (MeHg) is a highly neurotoxic environmental pollutant. Even though molecular mechanisms mediating MeHg toxicity are not completely understood, several lines of evidence indicate that the neurotoxic effects resultant from MeHg exposure represent a consequence of its pro-oxidative properties. In this regard, MeHg is a soft electrophile that preferentially interacts with (and oxidize) nucleophilic groups (mainly thiols and selenols) from biomolecules, including proteins and low-molecular-weight molecules. Such interaction contributes to the occurrence of oxidative stress and impaired function of several molecules [proteins (receptors, transporters, enzymes, structural proteins), lipids (i.e., membrane constituents and intracellular messengers), and nucleic acids (i.e., DNA)], culminating in neurotoxicity.In this chapter, an initial background on the general aspects regarding the neurotoxicology of MeHg, with a particular focus on its pro-oxidative properties and its interaction with nucleophilic thiol- and selenol-containing molecules, is provided. Even though experimental evidence indicates that symptoms (i.e., motor impairment) resultant from MeHg exposure are linked to its pro-oxidative properties, as well as to their molecular consequences (lipid peroxidation, disruption of glutamate and/or calcium homeostasis, etc.), data concerning the relationship between molecular parameters and behavioral impairment others that those related to the motor function (i.e., visual impairment, cognitive skills, etc.) are scarce. Thus, even though scientific research has provided a significant amount of knowledge concerning the mechanisms mediating MeHg-induced neurotoxicity in the last decades, the whole scenario is far from being completely understood, and further research in this area is well warranted.
甲基汞（MeHg）是一种具有高度神经毒性的环境污染物。尽管介导甲基汞毒性的分子机制尚未完全明确，但有几条证据表明，甲基汞暴露所产生的神经毒性效应是其促氧化特性的结果。在这方面，甲基汞是一种软亲电试剂，它优先与生物分子（包括蛋白质和低分子量分子）中的亲核基团（主要是硫醇和硒醇）相互作用（并将其氧化）。这种相互作用会导致氧化应激的发生以及多种分子[蛋白质（受体、转运蛋白、酶、结构蛋白）、脂质（即膜成分和细胞内信使）和核酸（即DNA）]功能受损，最终导致神经毒性。在本章中，我们将介绍甲基汞神经毒理学的一般背景知识，特别关注其促氧化特性以及与含亲核硫醇和硒醇分子的相互作用。尽管实验证据表明，甲基汞暴露所导致的症状（即运动功能障碍）与其促氧化特性及其分子后果（脂质过氧化、谷氨酸和/或钙稳态破坏等）有关，但关于分子参数与运动功能以外的行为障碍（即视力障碍、认知技能等）之间关系的数据却很稀少。因此，尽管在过去几十年里，科学研究已经提供了大量关于介导甲基汞诱导神经毒性机制的知识，但整个情况远未完全明了，该领域的进一步研究很有必要。
