β-N-methylamino-L-alanine Enhances Neurotoxicity Through Multiple Mechanisms

The idea that the environmental toxin β-N-methylamino-L-alanine (BMAA) is involved in neurodegenerative diseases on Guam has risen and NOT THE PUBLISHED VERSION; this is the author’s final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page. Neurobiology of Disease, Vol. 25, No. 2 (February 2007): pg. 360-366. DOI. This article is © Elseiver and permission has been granted for this version to appear in e-Publications@Marquette. Elsevier does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from Elsevier. 2 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 μM 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 three fold: 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.