Current Environmental Health Reports

, Volume 4, Issue 2, pp 200–207 | Cite as

Evaluating a Gene-Environment Interaction in Amyotrophic Lateral Sclerosis: Methylmercury Exposure and Mutated SOD1

  • Jordan M. Bailey
  • Alexandra Colón-Rodríguez
  • William D. AtchisonEmail author
Mechanisms of Toxicity (JR Richardson, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Mechanisms of Toxicity


Purpose of Review

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 Findings

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.


Amyotrophic lateral sclerosis Gene-environment (GxE) interaction Methylmercury AMPA receptor Glutamate Calcium homeostasis 



Gene-environment interaction


Amyotrophic lateral sclerosis


Sporadic amyotrophic lateral sclerosis


Familial amyotrophic lateral sclerosis


Superoxide dismutase 1


Fused in sarcoma/translocated in sarcoma


TAR DNA-binding protein 43


Chromosome 9 open reading frame 72


Motor neuron


Coproporphyrinogen oxidase 4


Brain-derived neurotrophic factor




Single nucleotide polymorphisms




Internal calcium concentration




α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid


Reactive oxygen species


Excitatory amino acid transporter




1-Naphthyl acetyl spermine


AMPA receptor subunit 2


Adenosine deaminase acting on RNA



Supported by grants NIEHS T32 ES00725527 (Jordan M. Bailey, Alexandra Colón-Rodríguez) and NIH Grant R01 ES024064 (Jordan M. Bailey, Alexandra Colón-Rodríguez, William D. Atchison).

Compliance with Ethical Standards

Conflict of Interest

Jordan M. Bailey, Alexandra Colón-Rodríguez, and William D. Atchison declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Jordan M. Bailey
    • 1
    • 2
  • Alexandra Colón-Rodríguez
    • 1
    • 2
    • 3
  • William D. Atchison
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of Pharmacology and ToxicologyMichigan State UniversityEast LansingUSA
  2. 2.Institute for Integrative ToxicologyMichigan State UniversityEast LansingUSA
  3. 3.Comparative Medicine and Integrative Biology ProgramMichigan State UniversityEast LansingUSA
  4. 4.East LansingUSA

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