BMAA, Neurodegeneration, and Neuroprotection.

In this volume, studies springing from a BMAA symposium held in Salt Lake City, Utah, in April 2019 are presented. Although most studies of neurotoxicity consider the effects of BMAA as an isolated molecule, it is now known that environmental exposures can be to a combination of BMAA-related molecules, including enantiomers, isomers, other co-occurring cyanotoxins, and BMAA carbamates. Within the body, BMAA may exist in equilibrium with α- and β-carbamates formed in the presence of bicarbonate. BMAA and its isomers 2,4-DAB and AEG, accumulate over decades in biocrusts and persist at depths in soil profiles of the Gulf deserts. In Florida, releases of cyanobacterially ladened water from Lake Okeechobee can extend into coastal environments where diatoms and possibly dinoflagellates also produce BMAA and isomers in addition to brevetoxins. Along the African Lake Chad, neurotoxic risks from consumption of dried cyanobacterial cakes may, however, be outweighed by their amino acid addition to otherwise protein-deficient diets. Discrepancies in the detection and quantification of BMAA from different laboratories likely originate in the use of different analytical methods. C-18 columns, used to study derivatized BMAA, can efficiently separate BMAA from its isomers in validated methods, while validation is not possible for HILIC columns in the study of underivatized BMAA, since they do not adequately separate BMAA from its isomer BAMA. The presence of BMAA dimers, metal adducts, and carbamates may result in underestimation of BMAA by mass spectrometry. BMAA research led to the identification of the dietary amino acid L-serine as a neuroprotective molecule. In animal and clinical trials, L-serine appears to slow neurodegeneration, although the modes of action are still under study. Based on zebra fish sensitivity to platinum-based chemotherapeutic agents, investigators have found that L-serine reduces reactive oxygen species (ROS) but does not protect auditory hybridoma cells from cisplatin. Another possible mode of action of L-serine, induction of autophagic-lysosomal enzymes, is also being explored. The hypothesis that cyanobacterial exposures in general, and chronic exposures to BMAA in particular, may prove to be risk factors for neurodegenerative illnesses has not been without critics. Emerging from the symposium, a multi-authored response to one such critical paper appears in this collection of articles. Instead of waiting until there is a conclusive proof of risk, the adoption of the "precautionary default principle," proposed by Ingvar Brandt and his colleagues in Sweden, is suggested. Avoidance of exposures to cyanobacterial blooms and other sources of BMAA is suggested, until further research indicates such precautions to be unnecessary. [ABSTRACT FROM AUTHOR]