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Neurotoxicity Research

, Volume 36, Issue 3, pp 602–611 | Cite as

The Cyanotoxin and Non-protein Amino Acid β-Methylamino-L-Alanine (L-BMAA) in the Food Chain: Incorporation into Proteins and Its Impact on Human Health

  • Rachael A. DunlopEmail author
  • Gilles J. Guillemin
Review Article

Abstract

The size and frequency of cyanobacterial blooms are increasing concomitantly with rising global temperatures and increased eutrophication, and this has implications for human health. Cyanotoxins, including L-BMAA, have been implicated in triggering neurodegenerative diseases such as ALS/PDC and Alzheimer’s disease. L-BMAA is a water-soluble non-protein amino acid that can bioaccumulate up the food chain, in a free- and protein-bound form. While some data exists on the degree of environmental enrichment of L-BMAA in water bodies, cyanobacteria-derived supplements, fruit bats, and seafood, virtually nothing is known about the presence of L-BMAA in other foodstuffs. It has now been shown several times in laboratory settings that plants can absorb L-BMAA into their leaves and stems, but data from wild-grown plants is nascent. One of the mechanisms implicated in L-BMAA bioaccumulation is misincorporation into proteins in the place of the canonical amino acid L-serine. We first identified this as a mechanism of action of L-BMAA in 2013, and since then, several groups have replicated these findings, but others have not. Here, we discuss in detail the experimental approaches, why they may have produced negative findings and propose several ways forward for developing consistency within the field. We emphasize the need to standardize cell culture methods, using L-serine-free medium to study misincorporation of BMAA, and urge accurate reporting of the components present in cell culture media.

Keywords

L-BMAA L-serine Misincorporation Protein incorporation Cyanobacteria Cyanotoxins Neurodegeneration 

Abbreviations

AD

Alzheimer’s disease

AEG

N-(2-aminoethyl) glycine

ALS

Amyotrophic lateral sclerosis

ALS/PDC

Amyotrophic lateral sclerosis-parkinsonism-dementia type complex

AQC

6-Aminoquinolyl-N-hydroxysccinimidyl carbamate

L-BMAA

β-methylamino-L-alanine

D-BMAA

β-methylamino-D-alanine

CHX

cycloheximide

DAB

2,4-Diaminobutyric acid

DHFR

dihydrofolate reductase

DTT

dithiothreitol

HBSS

Hank’s buffered salt solution

HCl

Hydrochloric acid

HILIC

Hydrophilic interaction liquid chromatography

HPLC/MS-MS

High-performance liquid chromatography with tandem mass spectrometry

LC-MS/MS

Liquid chromatography and tandem mass spectrometry

MND

Motor neuron disease

mRNA

messenger RNA

SDS

sodium-dodecyl sulfate

SDS-PAGE

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

TCA

trichloroacetic acid

Notes

Acknowledgments

The authors thank Ms. Gracie McKanna for producing Fig. 1, Dr. Paul A. Cox for careful editing of this manuscript and Dr. Sandra Banack for her input.

Funding Information

Professor Guillemin is funded by the Australian Research Council, Deb Bailey Foundation, MND and Me Foundation, Fight MND Foundation and Macquarie University. Doctor Rachael Dunlop’s research was funded, in part, by an equipment grant from The William Stamps Farish Fund.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Brain Chemistry LabsInstitute for EthnomedicineJacksonUSA
  2. 2.Macquarie University Centre for MND Research, Department of Biological Sciences, Faculty of Medicine and Health SciencesMacquarie UniversitySydneyAustralia

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