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      Occurrence of β- N-methylamino-l-alanine (BMAA) and Isomers in Aquatic Environments and Aquatic Food Sources for Humans

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          Abstract

          The neurotoxin β- N-methylamino- l-alanine (BMAA), a non-protein amino acid produced by terrestrial and aquatic cyanobacteria and by micro-algae, has been suggested to play a role as an environmental factor in the neurodegenerative disease Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia complex (ALS-PDC). The ubiquitous presence of BMAA in aquatic environments and organisms along the food chain potentially makes it public health concerns. However, the BMAA-associated human health risk remains difficult to rigorously assess due to analytical challenges associated with the detection and quantification of BMAA and its natural isomers, 2,4-diamino butyric acid (DAB), β-amino- N-methyl-alanine (BAMA) and N-(2-aminoethyl) glycine (AEG). This systematic review, reporting the current knowledge on the presence of BMAA and isomers in aquatic environments and human food sources, was based on a selection and a score numbering of the scientific literature according to various qualitative and quantitative criteria concerning the chemical analytical methods used. Results from the best-graded studies show that marine bivalves are to date the matrix containing the higher amount of BMAA, far more than most fish muscles, but with an exception for shark cartilage. This review discusses the available data in terms of their use for human health risk assessment and identifies knowledge gaps requiring further investigations.

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          Diverse taxa of cyanobacteria produce beta-N-methylamino-L-alanine, a neurotoxic amino acid.

          Cyanobacteria can generate molecules hazardous to human health, but production of the known cyanotoxins is taxonomically sporadic. For example, members of a few genera produce hepatotoxic microcystins, whereas production of hepatotoxic nodularins appears to be limited to a single genus. Production of known neurotoxins has also been considered phylogenetically unpredictable. We report here that a single neurotoxin, beta-N-methylamino-L-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanobacteria. The ubiquity of cyanobacteria in terrestrial, as well as freshwater, brackish, and marine environments, suggests a potential for wide-spread human exposure.
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            The Non-Protein Amino Acid BMAA Is Misincorporated into Human Proteins in Place of l-Serine Causing Protein Misfolding and Aggregation

            Mechanisms of protein misfolding are of increasing interest in the aetiology of neurodegenerative diseases characterized by protein aggregation and tangles including Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), Lewy Body Dementia (LBD), and Progressive Supranuclear Palsy (PSP). Some forms of neurodegenerative illness are associated with mutations in genes which control assembly of disease related proteins. For example, the mouse sticky mutation sti, which results in undetected mischarging of tRNAAla with serine resulting in the substitution of serine for alanine in proteins causes cerebellar Purkinje cell loss and ataxia in laboratory animals. Replacement of serine 422 with glutamic acid in tau increases the propensity of tau aggregation associated with neurodegeneration. However, the possibility that environmental factors can trigger abnormal folding in proteins remains relatively unexplored. We here report that a non-protein amino acid, β-N-methylamino-L-alanine (BMAA), can be misincorporated in place of l-serine into human proteins. We also report that this misincorporation can be inhibited by l-serine. Misincorporation of BMAA into human neuroproteins may shed light on putative associations between human exposure to BMAA produced by cyanobacteria and an increased incidence of ALS.
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              Transfer of a cyanobacterial neurotoxin within a temperate aquatic ecosystem suggests pathways for human exposure.

              beta-methylamino-L-alanine (BMAA), a neurotoxic nonprotein amino acid produced by most cyanobacteria, has been proposed to be the causative agent of devastating neurodegenerative diseases on the island of Guam in the Pacific Ocean. Because cyanobacteria are widespread globally, we hypothesized that BMAA might occur and bioaccumulate in other ecosystems. Here we demonstrate, based on a recently developed extraction and HPLC-MS/MS method and long-term monitoring of BMAA in cyanobacterial populations of a temperate aquatic ecosystem (Baltic Sea, 2007-2008), that BMAA is biosynthesized by cyanobacterial genera dominating the massive surface blooms of this water body. BMAA also was found at higher concentrations in organisms of higher trophic levels that directly or indirectly feed on cyanobacteria, such as zooplankton and various vertebrates (fish) and invertebrates (mussels, oysters). Pelagic and benthic fish species used for human consumption were included. The highest BMAA levels were detected in the muscle and brain of bottom-dwelling fishes. The discovery of regular biosynthesis of the neurotoxin BMAA in a large temperate aquatic ecosystem combined with its possible transfer and bioaccumulation within major food webs, some ending in human consumption, is alarming and requires attention.
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                14 February 2018
                February 2018
                : 10
                : 2
                : 83
                Affiliations
                [1 ]UMR SEBIO, Bat 18, Campus du Moulin de la Housse, BP 1039, 51687 REIMS CEDEX 2, France
                [2 ]ANSES—French Agency for Food, Environmental and Occupational Health & Safety, Direction de l’Evaluation des Risques, 14 rue, Pierre et Marie Curie, 94701 Maisons-Alfort, France; nathalie.arnich@ 123456anses.fr (N.A.), thomas.maignien@ 123456anses.fr (T.M.)
                [3 ]Université Paris-Est, ANSES, Laboratory for Food Safety, F94701 Maisons-Alfort, France; ronel.bire@ 123456anses.fr
                Author notes
                [* ]Correspondence: emilie.lance@ 123456univ-reims.fr ; Tel.: +33-326-913-369
                Author information
                https://orcid.org/0000-0003-1731-0390
                Article
                toxins-10-00083
                10.3390/toxins10020083
                5848184
                29443939
                5e8571df-e90d-4989-bcec-96416ffe0a07
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 December 2017
                : 08 February 2018
                Categories
                Review

                Molecular medicine
                bmaa,seafood,freshwater foodweb,human health risk assessment,analytical methods
                Molecular medicine
                bmaa, seafood, freshwater foodweb, human health risk assessment, analytical methods

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