Beta-N-methylamino-L-alanine enhances neurotoxicity through multiple mechanisms

Neurobiol Dis. 2007 Feb;25(2):360-6. doi: 10.1016/j.nbd.2006.10.002. Epub 2006 Nov 13.

Abstract

The idea that the environmental toxin beta-N-methylamino-l-alanine (BMAA) is involved in neurodegenerative diseases on Guam has risen and fallen over the years. The theory has gained greater interest with recent reports that BMAA is biomagnified, is widely distributed around the planet, and is present in the brains of Alzheimer's patients in Canada. We provide two important new findings. First, we show that BMAA at concentrations as low as 10 muM can potentiate neuronal injury induced by other insults. This is the first evidence that BMAA at concentrations below the mM range can enhance death of cortical neurons and illustrates potential synergistic effects of environmental toxins with underlying neurological conditions. Second, we show that the mechanism of BMAA toxicity is threefold: it is an agonist for NMDA and mGluR5 receptors, and induces oxidative stress. The results provide further support for the hypothesis that BMAA plays a role in neurodegenerative diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids, Diamino / toxicity*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Cells, Cultured
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cyanobacteria Toxins
  • Excitatory Amino Acid Agonists / toxicity*
  • Hazardous Substances / toxicity
  • Mice
  • Nerve Degeneration / chemically induced*
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neurodegenerative Diseases / chemically induced*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neurotoxins / toxicity
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Patch-Clamp Techniques
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Amino Acids, Diamino
  • Cyanobacteria Toxins
  • Excitatory Amino Acid Agonists
  • Grm5 protein, mouse
  • Hazardous Substances
  • Neurotoxins
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • beta-N-methylamino-L-alanine