Redox state in mediating methylmercury neurotoxicity

Methylmercury (MeHg) is an environmental pollutant that has been reported to induce neurotoxicity in both animals and humans. Although the molecular mechanisms underlying MeHg toxicity remain elusive, several lines of evidence indicate that MeHg is able to change the redox state of particular redox couples (i.e., reduced/oxidized glutathione (GSH), reduced/oxidized sulfhydryl or selenohydryl proteins, etc.), thus changing the entire cellular redox environment. These events contribute to oxidative stress, which culminates in neurotoxicity. Although MeHg-induced changes in the redox state are related to its direct interactions with nucleophilic molecules, such as GSH or sulfhydryl/selenohydryl proteins, it is noteworthy that MeHg can cause neurotoxicity even when present in concentrations 100- to 1,000fold less than those of these nucleophiles. Accordingly, recent evidence indicates that specific nucleophilic molecules (not yet fully identified) are primarily and/or preferentially targeted by MeHg due to their particular high reactivity toward this toxicant, thus initiating a cascade of molecular events that culminate in neurotoxicity. In this chapter, we give an initial background on the general concepts regarding the redox state and its important role in counteracting oxidative stress in the central nervous system, followed by discussions on the potential interaction of MeHg with redox couplers (mainly nucleophilic thiol- and selenol-containing molecules).