The importance of glutamate, glycine, and γ-aminobutyric acid transport and regulation in manganese, mercury and lead neurotoxicity

Vanessa A. Fitsanakis, Michael Aschner

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Historically, amino acids were studied in the context of their importance in protein synthesis. In the 1950s, the focus of research shifted as amino acids were recognized as putative neurotransmitters. Today, many amino acids are considered important neurochemicals. Although many amino acids play a role in neurotransmission, glutamate (Glu), glycine (Gly), and γ-aminobutyric acid (GABA) are among the more prevalent and better understood. Glu, the major excitatory neurotransmitter, and Gly and GABA, the major inhibitory neurotransmitters, in the central nervous system, are known to be tightly regulated. Prolonged exposure to environmental toxicants, such as manganese (Mn), mercury (Hg), or lead (Pb), however, can lead to dysregulation of these neurochemicals and subsequent neurotoxicity. While the ability of these metals to disrupt the regulation of Glu, Gly and GABA have been studied, few articles have examined the collective role of these amino acids in the respective metal's mechanism of toxicity. For each of the neurotransmitters above, we will provide a brief synopsis of their regulatory function, including the importance of transport and re-uptake in maintaining their optimal function. Additionally, the review will address the hypothesis that aberrant homeostasis of any of these amino acids, or a combination of the three, plays a role in the neurotoxicity of Mn, Hg, or Pb.

Original languageEnglish (US)
Pages (from-to)343-354
Number of pages12
JournalToxicology and Applied Pharmacology
Volume204
Issue number3
DOIs
StatePublished - 2005
Externally publishedYes

Fingerprint

Aminobutyrates
Manganese
Mercury
Glycine
Glutamic Acid
Amino Acids
Neurotransmitter Agents
Metals
Environmental Exposure
Neurology
Synaptic Transmission
Toxicity
Lead
Homeostasis
Central Nervous System
Research
Proteins

Keywords

  • γ-aminobutyric acid
  • Glutamate
  • Glycine

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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