title: Evaluating a Gene-Environment Interaction in Amyotrophic Lateral Sclerosis: Methylmercury Exposure and Mutated SOD1.
abstract: Gene-environment (GxE) interactions likely contribute to numerous diseases, but are often difficult to model in the laboratory. Such interactions have been widely hypothesized for amyotrophic lateral sclerosis (ALS); recent controlled laboratory studies are discussed here and hypotheses related to possible mechanisms of action are offered. Using methylmercury exposure and mutated SOD1 to model the impacts of such an interaction, we interpret evidence about their respective mechanisms of toxicity to interrogate the possibility of additive (or synergistic) effects when combined.
  
  
  
  Recent work has converged on mechanisms of calcium-mediated glutamate excitotoxicity as a likely contributor in one model of a gene-environment interaction affecting the onset and progression of ALS-like phenotype. The current experimental literature on mechanisms of metal-induced neuronal injury and their relevant interactions with genetic contributions in ALS is sparse, but we describe those studies here and offer several integrative hypotheses about the likely mechanisms involved.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, 48824-1317, USA.|Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824-1317, USA.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Bailey
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, 48824-1317, USA.|Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824-1317, USA.|Comparative Medicine and Integrative Biology Program, Michigan State University, East Lansing, MI, 48824-1317, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Colón-Rodríguez
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, 48824-1317, USA. atchiso1@msu.edu.|Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824-1317, USA. atchiso1@msu.edu.|Comparative Medicine and Integrative Biology Program, Michigan State University, East Lansing, MI, 48824-1317, USA. atchiso1@msu.edu.|, Life Science Building, 1355 Bogue St. Room B331A, East Lansing, MI, 48824-1317, USA. atchiso1@msu.edu.
authors.forename: William D
authors.initials: WD
authors.lastname: Atchison
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced / Q000503:physiopathology*; D002118:Calcium; D016166:Free Radical Scavengers; D059647:Gene-Environment Interaction; D018698:Glutamic Acid; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity*; D018091:Receptors, AMPA; D013482:Superoxide Dismutase / Q000633:toxicity*
chemical_list: D016166:Free Radical Scavengers; D008767:Methylmercury Compounds; D018091:Receptors, AMPA; D018698:Glutamic Acid; D013482:Superoxide Dismutase; D002118:Calcium
keywords: AMPA receptor; Amyotrophic lateral sclerosis; Calcium homeostasis; Gene-environment (GxE) interaction; Glutamate; Methylmercury