Methylmercury-induced neurotoxicity and apoptosis.
Methylmercury is a widely distributed environmental toxicant with detrimental effects on the developing and adult nervous system. Due to its accumulation in the food chain, chronic exposure to methylmercury via consumption of fish and sea mammals is still a major concern for human health, especially developmental exposure that may lead to neurological alterations, including cognitive and motor dysfunctions. Mercury-induced neurotoxicity and the identification of the underlying mechanisms has been a main focus of research in the neurotoxicology field. Three major mechanisms have been identified as critical in methylmercury-induced cell damage including (i) disruption of calcium homeostasis, (ii) induction of oxidative stress via overproduction of reactive oxygen species or reduction of antioxidative defenses and (iii) interactions with sulfhydryl groups. In vivo and in vitro studies have provided solid evidence for the occurrence of neural cell death, as well as cytoarchitectural alterations in the nervous system after exposure to methylmercury. Signaling cascades leading to cell death induced by methylmercury involve the release of mitochondrial factors, such as cytochrome c and AIF with subsequent caspase-dependent or -independent apoptosis, respectively; induction of calcium-dependent proteases calpains; interaction with lysosomes leading to release of cathepsins. Interestingly, several pathways can be activated in parallel, depending on the cell type. In this paper, we provide an overview of recent findings on methylmercury-induced neurotoxicity and cell death pathways that have been described in neural and endocrine cell systems.
Ceccatelli
Sandra
S
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Sandra.Ceccatelli@ki.se
Daré
Elisabetta
E
Moors
Michaela
M
D000818:Animals; D017209:Apoptosis; D004703:Endocrine System / Q000187:drug effects; D006801:Humans; D008767:Methylmercury Compounds / Q000378:metabolism / Q000633:toxicity*; D009420:Nervous System / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D008767:Methylmercury Compounds