Neurotoxicity of isomers of the environmental toxin L-BMAA. (September 2020)

• Record Type: Journal Article
• Authors: Schneider, Thomas; Simpson, Catherine; Desai, Prachi; Tucker, Madeleine; Lobner, Doug
• Is Part Of: Toxicon. Volume 184(2020)
• Page Start: 175
• Page End: 179
• Publication Date: 2020-09
• Subjects: β-N-Methylamino-L-alanine -- Neurotoxin -- Oxidative stress -- Cyanobacteria; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2020.06.014
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: There is evidence that the environmental toxin β-N-methylamino-L-alanine (L-BMAA) may be involved in neurodegenerative diseases. However, a number of controversies exist regarding L-BMAA, one of which is the possibility that when assaying for L-BMAA, its isomers are being detected instead. There are at least four isomers of BMAA that are known to occur: L-BMAA, β-N-methylamino-D-alanine (D-BMAA), 2, 4-diaminobutyric acid (DAB), and N-(2-aminoethyl)glycine (AEG). The fact that isomers of BMAA exist in nature also leads to the possibility that they are involved in toxicity. We set out to determine both the potency and the mechanism of toxicity of L-BMAA, D-BMAA, DAB, asnd AEG using primary cortical cultures. The results were surprising with the following order of potency of toxicity: AEG > DAB > D-BMAA > L-BMAA. These results suggest that AEG may be an overlooked neurotoxin. We found that AEG induced toxicity through mGluR5 receptors and induction of oxidative stress. While the potential role of L-BMAA in neurodegenerative diseases has been emphasized, other isomers of L-BMAA, particularly AEG, are actually more potent toxins, and could therefore potentially contribute to neurodegenerative diseases. Highlights: Isomers of L-BMAA are more potent neurotoxins than L-BMAA. AEG is the most potent neurotoxic isomer of L-BMAA. The neurotoxicity of L-BMAA and AEG are consistent with them acting on system xc -to inhibit cystine uptake.