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Cyanobacterial Neurotoxins: Their Occurrence and Mechanisms of Toxicity

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Abstract

Cyanobacteria are some of the oldest organisms on earth, and have evolved to produce a battery of toxic metabolites, including hepatotoxins, dermatoxins, and neurotoxins. In this review, we focus on the occurrence and mechanisms of toxicity of a number of neurotoxins synthesised by these ancient photosynthetic prokaryotes. We discuss the evidence linking β-methylamino-L-alanine (BMAA), a non-protein amino acid, to an unusual neurological disease complex reported on the island of Guam in the 1950s, and how 60 years later, the role that BMAA plays in human disease is still unclear. There is now evidence that BMAA is also produced by some eukaryotes, and can bioaccumulate in food chains; this combined with higher frequency of cyanobacterial blooms globally, increases the potential for human exposure. Three BMAA isomers that often co-occur with BMAA have been identified, and the current knowledge on the toxicity of these molecules is presented. The acute alkaloid toxins; anatoxin-a, homoanatoxin-a and the saxitoxins, and the organophosphate neurotoxin anatoxin-a(S) are also discussed. In many cases, human exposure to a cocktail of cyanobacterial neurotoxins is likely; however, the implications of combined exposure to these toxins have not been fully explored. Increased understanding of the combined effects of cyanobacterial neurotoxins is required to fully understand how these molecules impact on human health.

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References

  • Al-Sammak MA, Hoagland KD, Cassada D, Snow DD (2014) Co-occurrence of the cyanotoxins BMAA, DABA and anatoxin-a in Nebraska reservoirs, fish, and aquatic plants. Toxins (Basel) 6(2):488–508. doi:10.3390/toxins6020488

  • Al-Sammak MA, Hoagland KD, Snow DD, Cassada D (2015) Methods for simultaneous detection of the cyanotoxins BMAA, DABA, and anatoxin-a in environmental samples. Toxicon 2015:1–9

    Article  Google Scholar 

  • Araoz R, Molgo J, Tandeau de Marsac N (2010) Neurotoxic cyanobacterial toxins. Toxicon 56(5):813–828

    Article  CAS  PubMed  Google Scholar 

  • Arif M, Kazim SF, Grundke-Iqbal I, Garruto RM, Iqbal K (2014) Tau pathology involves protein phosphatase 2A in parkinsonism-dementia of Guam. Proc Natl Acad Sci U S A 111(3):1144–1149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banack SA, Cox PA (2003) Biomagnification of cycad neurotoxins in flying foxes: implications for ALS-PDC in Guam. Neurology 61(3):387–389

    Article  CAS  PubMed  Google Scholar 

  • Banack SA, Cox PA, Murch SJ (2009) Flying fox consumption and human neurodegenerative disease in Guam (Chapter 12). In: Fleming TH, Racey PA (eds) Island bats: ecology, evolution, and conservation, vol chapter 12. University of Chicago Press, Chicago

    Google Scholar 

  • Banack SA, Metcalf JS, Spacil Z, Downing TG, Downing S, Long A, Nunn PB, Cox PA (2011) Distinguishing the cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) from other diamino acids. Toxicon 57(5):730–738

    Article  CAS  PubMed  Google Scholar 

  • Banack SA, Metcalf JS, Jiang L, Craighead D, Ilag LL, Cox PA (2012) Cyanobacteria produce N-(2-aminoethyl)glycine, a backbone for peptide nucleic acids which may have been the first genetic molecules for life on Earth. PLoS One 7 (11):e49043. doi:10.1371/journal.pone.0049043

  • Banack SA, Metcalf JS, Bradley WG, Cox PA (2014) Detection of cyanobacterial neurotoxin beta-N-methylamino-l-alanine within shellfish in the diet of an ALS patient in Florida. Toxicon 90:167–173

    Article  CAS  PubMed  Google Scholar 

  • Berry JP, Gantar M, Perez MH, Berry G, Noriega FG (2008) Cyanobacterial toxins as allelochemicals with potential applications as algaecides, herbicides and insecticides. Mar Drugs 6(2):117–146. doi:10.3390/md20080007

  • Berntzon L, Ronnevi LO, Bergman B, Eriksson J (2015) Detection of BMAA in the human central nervous system. Neuroscience 292:137–147

    Article  CAS  PubMed  Google Scholar 

  • Boopathi T, Ki JS (2014) Impact of environmental factors on the regulation of cyanotoxin production. Toxins (Basel) 6(7):1951–1978

    Article  Google Scholar 

  • Brand LE, Pablo J, Compton A, Hammerschlag N, Mash DC (2010) Cyanobacterial blooms and the occurrence of the neurotoxin beta-N-methylamino-L-alanine (BMAA) in South Florida aquatic food webs. Harmful Algae 9(6):620–635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brenner ED, Stevenson DW, McCombie RW, Katari MS, Rudd SA, Mayer KF, Palenchar PM, Runko SJ, Twigg RW, Dai G, Martienssen RA, Benfey PN, Coruzzi GM (2003) Expressed sequence tag analysis in Cycas, the most primitive living seed plant. Genome Biol 4(12):R78

    Article  PubMed  PubMed Central  Google Scholar 

  • Carey CC, Ibelings BW, Hoffmann EP, Hamilton DP, Brookes JD (2012) Eco-physiological adaptations that favour freshwater cyanobacteria in a changing climate. Water Res 46(5):1394–1407. d

    Article  CAS  PubMed  Google Scholar 

  • Chen CH, Flory W, Koeppe RE (1972) Variation of neurotoxicity of L- and D-2,4-diaminobutyric acid with route of administration. Toxicol Appl Pharmacol 23(2):334–338

    Article  CAS  PubMed  Google Scholar 

  • Clemente Z, Busato RH, Oliveira Ribeiro CA, Cestari MM, Ramsdorf WA, Magalhaes VF, Wosiack AC, Silva de Assis HC (2010) Analyses of paralytic shellfish toxins and biomarkers in a southern Brazilian reservoir. Toxicon 55(2–3):396–406

    Article  CAS  PubMed  Google Scholar 

  • Combes A, El Abdellaoui S, Sarazin C, Vial J, Mejean A, Ploux O, Pichon V, group B (2013) Validation of the analytical procedure for the determination of the neurotoxin beta-N-methylamino-L-alanine in complex environmental samples. Anal Chim Acta 771:42–49

    Article  CAS  PubMed  Google Scholar 

  • Corbel S, Mougin C, Bouaicha N (2014) Cyanobacterial toxins: modes of actions, fate in aquatic and soil ecosystems, phytotoxicity and bioaccumulation in agricultural crops. Chemosphere 96:1–15

    Article  CAS  PubMed  Google Scholar 

  • Cox PA, Sacks OW (2002) Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam. Neurology 58(6):956–959

    Article  PubMed  Google Scholar 

  • Cox PA, Banack SA, Murch SJ (2003) Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam. Proc Natl Acad Sci U S A 100(23):13380–13383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox PA, Banack SA, Murch SJ, Rasmussen U, Tien G, Bidigare RR, Metcalf JS, Morrison LF, Codd GA, Bergman B (2005) Diverse taxa of cyanobacteria produce beta-N-methylamino-L-alanine, a neurotoxic amino acid. Proc Natl Acad Sci U S A 102(14):5074–5078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox PA, Richer R, Metcalf JS, Banack SA, Codd GA, Bradley WG (2009) Cyanobacteria and BMAA exposure from desert dust: a possible link to sporadic ALS among Gulf War veterans. Amyotroph Lateral Scler 10(Suppl 2):109–117

    Article  CAS  PubMed  Google Scholar 

  • Cox PA, Davis DA, Mash DC, Metcalf JS, Banack SA (2016) Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain. Proc Biol Sci 283(1823)

  • Cruz-Aguado R, Winkler D, Shaw CA (2006) Lack of behavioral and neuropathological effects of dietary beta-methylamino-L-alanine (BMAA) in mice. Pharmacol Biochem Behav 84(2):294–299

    Article  CAS  PubMed  Google Scholar 

  • Di Rienzi SC, Sharon I, Wrighton KC, Koren O, Hug LA, Thomas BC, Goodrich JK, Bell JT, Spector TD, Banfield JF, Ley RE (2013) The human gut and groundwater harbor non-photosynthetic bacteria belonging to a new candidate phylum sibling to Cyanobacteria. elife 2:e01102

    Article  PubMed  PubMed Central  Google Scholar 

  • Downing S, Downing TG (2016) The metabolism of the non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) in the cyanobacterium Synechocystis PCC6803. Toxicon 115:41–48

    Article  CAS  PubMed  Google Scholar 

  • Downing S, Banack SA, Metcalf JS, Cox PA, Downing TG (2011) Nitrogen starvation of cyanobacteria results in the production of beta-N-methylamino-L-alanine. Toxicon 58(2):187–194

    Article  CAS  PubMed  Google Scholar 

  • Dunlop RA, Cox PA, Banack SA, Rodgers KJ (2013) The non-protein amino acid BMAA is misincorporated into human proteins in place of l-serine causing protein misfolding and aggregation. PLoS One 8(9):e75376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dziallas C, Grossart HP (2011) Increasing oxygen radicals and water temperature select for toxic Microcystis sp. PLoS One 6(9):e25569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Shehawy R, Gorokhova E, Fernandez-Pinas F, del Campo FF (2012) Global warming and hepatotoxin production by cyanobacteria: what can we learn from experiments? Water Res 46(5):1420–1429

    Article  CAS  PubMed  Google Scholar 

  • Esterhuizen M, Downing TG (2008) Beta-N-methylamino-L-alanine (BMAA) in novel South African cyanobacterial isolates. Ecotoxicol Environ Saf 71(2):309–313

    Article  CAS  PubMed  Google Scholar 

  • Faassen EJ, Gillissen F, Lurling M (2012) A comparative study on three analytical methods for the determination of the neurotoxin BMAA in cyanobacteria. PLoS One 7(5):e36667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrao-Filho Ada S, Kozlowsky-Suzuki B (2011) Cyanotoxins: bioaccumulation and effects on aquatic animals. Mar Drugs 9(12):2729–2772. doi:10.3390/md9122729

    Article  PubMed  Google Scholar 

  • Garruto RM, Gajdusek C, Chen KM (1980) Amyotrophic lateral sclerosis among Chamorro migrants from Guam. Ann Neurol 8(6):612–619

    Article  CAS  PubMed  Google Scholar 

  • Garruto RM, Gajdusek DC, Chen KM (1981) Amyotrophic lateral sclerosis and parkinsonism-dementia among Filipino migrants to Guam. Ann Neurol 10(4):341–350

    Article  CAS  PubMed  Google Scholar 

  • Glover WB, Mash DC, Murch SJ (2014) The natural non-protein amino acid N-beta-methylamino-L-alanine (BMAA) is incorporated into protein during synthesis. Amino Acids 46(11):2553–2559

    Article  CAS  PubMed  Google Scholar 

  • Hammerschlag N, Davis DA, Mondo K, Seely MS, Murch SJ, Glover WB, Divoll T, Evers DC, Mash DC (2016) Cyanobacterial neurotoxin BMAA and mercury in sharks. Toxins (Basel) 8(8)

  • Jiang L, Aigret B, De Borggraeve WM, Spacil Z, Ilag LL (2012) Selective LC-MS/MS method for the identification of BMAA from its isomers in biological samples. Anal Bioanal Chem 403(6):1719–1730

    Article  CAS  PubMed  Google Scholar 

  • Jiang L, Eriksson J, Lage S, Jonasson S, Shams S, Mehine M, Ilag LL, Rasmussen U (2014a) Diatoms: a novel source for the neurotoxin BMAA in aquatic environments. PLoS One 9(1):e84578

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang L, Kiselova N, Rosen J, Ilag LL (2014b) Quantification of neurotoxin BMAA (beta-N-methylamino-L-alanine) in seafood from Swedish markets. Sci Rep 4:6931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiao Y, Chen Q, Chen X, Wang X, Liao X, Jiang L, Wu J, Yang L (2014) Occurrence and transfer of a cyanobacterial neurotoxin beta-methylamino-l-alanine within the aquatic food webs of Gonghu Bay (Lake Taihu, China) to evaluate the potential human health risk. Sci Total Environ 468-469C:457–463

    Article  Google Scholar 

  • Johnston GA, Twitchin B (1977) Stereospecificity of 2,4-diaminobutyric acid with respect to inhibition of 4-aminobutyric acid uptake and binding. Br J Pharmacol 59(1):218–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jonasson S, Eriksson J, Berntzon L, Spacil Z, Ilag LL, Ronnevi LO, Rasmussen U, Bergman B (2010) Transfer of a cyanobacterial neurotoxin within a temperate aquatic ecosystem suggests pathways for human exposure. Proc Natl Acad Sci U S A 107(20):9252–9257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karamyan VT, Speth RC (2008) Animal models of BMAA neurotoxicity: a critical review. Life Sci 82(5–6):233–246

    Article  CAS  PubMed  Google Scholar 

  • Karlsson O, Lindquist NG, Brittebo EB, Roman E (2009) Selective brain uptake and behavioral effects of the cyanobacterial toxin BMAA (beta-N-methylamino-L-alanine) following neonatal administration to rodents. Toxicol Sci 109(2):286–295

    Article  CAS  PubMed  Google Scholar 

  • Karlsson O, Roman E, Berg AL, Brittebo EB (2011) Early hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (beta-N-methylamino-L-alanine) during the neonatal period. Behav Brain Res 219(2):310–320

    Article  CAS  PubMed  Google Scholar 

  • Koerner DR (1952) Amyotrophic lateral sclerosis on Guam. Ann Intern Med 37(6):1204–1220

    Article  CAS  PubMed  Google Scholar 

  • Kruger T, Monch B, Oppenhauser S, Luckas B (2010) LC-MS/MS determination of the isomeric neurotoxins BMAA (beta-N-methylamino-L-alanine) and DAB (2,4-diaminobutyric acid) in cyanobacteria and seeds of Cycas revoluta and Lathyrus latifolius. Toxicon 55 (2-3):547–557. doi:10.1016/j.toxicon.2009.10.009

  • Lage S, Costa PR, Moita T, Eriksson J, Rasmussen U, Rydberg SJ (2014) BMAA in shellfish from two Portuguese transitional water bodies suggests the marine dinoflagellate Gymnodinium catenatum as a potential BMAA source. Aquat Toxicol 152:131–138

    Article  CAS  PubMed  Google Scholar 

  • Li A, Tian Z, Li J, Yu R, Banack SA, Wang Z (2010) Detection of the neurotoxin BMAA within cyanobacteria isolated from freshwater in China. Toxicon 55(5):947–953

    Article  CAS  PubMed  Google Scholar 

  • Li A, Song J, Hu Y, Deng L, Ding L, Li M (2016) New typical vector of neurotoxin beta-N-methylamino-l-alanine (BMAA) in the marine benthic ecosystem. Mar Drugs 14(11)

  • Lobner D (2009) Mechanisms of beta-N-methylamino-L-alanine induced neurotoxicity. Amyotroph Lateral Scler 10(Suppl 2):56–60

    Article  CAS  PubMed  Google Scholar 

  • Main BJ, Dunlop RA, Rodgers KJ (2016) The use of l-serine to prevent beta-methylamino-l-alanine (BMAA)-induced proteotoxic stress in vitro. Toxicon 109:7–12

    Article  CAS  PubMed  Google Scholar 

  • Masseret E, Banack S, Boumediene F, Abadie E, Brient L, Pernet F, Juntas-Morales R, Pageot N, Metcalf J, Cox P, Camu W, French Network on ALSCD, Investigation (2013) Dietary BMAA exposure in an amyotrophic lateral sclerosis cluster from southern France. PLoS One 8(12):e83406

    Article  PubMed  PubMed Central  Google Scholar 

  • Metcalf JS, Banack SA, Lindsay J, Morrison LF, Cox PA, Codd GA (2008) Co-occurrence of beta-N-methylamino-L-alanine, a neurotoxic amino acid with other cyanobacterial toxins in British waterbodies, 1990–2004. Environ Microbiol 10(3):702–708

    Article  CAS  PubMed  Google Scholar 

  • Metcalf JS, Banack SA, Kotut K, Krienitz L, Codd GA (2013) Amino acid neurotoxins in feathers of the Lesser Flamingo, Phoeniconaias minor. Chemosphere 90(2):835–839. doi:10.1016/j.chemosphere.2012.09.094

  • Mondo K, Hammerschlag N, Basile M, Pablo J, Banack SA, Mash DC (2012) Cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) in shark fins. Mar Drugs 10(2):509–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mondo K, Broc Glover W, Murch SJ, Liu G, Cai Y, Davis DA, Mash DC (2014) Environmental neurotoxins beta-N-methylamino-l-alanine (BMAA) and mercury in shark cartilage dietary supplements. Food Chem Toxicol 70:26–32

    Article  CAS  PubMed  Google Scholar 

  • Montine TJ, Li K, Perl DP, Galasko D (2005) Lack of beta-methylamino-l-alanine in brain from controls, AD, or Chamorros with PDC. Neurology 65(5):768–769

    Article  CAS  PubMed  Google Scholar 

  • Mowe MAD, Mitrovic SM, Lim RP, Furey A, Yeo DCJ (2014) Tropical cyanobacterial blooms: a review of prevalence, problem taxa, toxins and influencing environmental factors. J Limnol 74(2):205–224

    Google Scholar 

  • de Munck E, Munoz-Saez E, Miguel BG, Solas MT, Ojeda I, Martinez A, Gil C, Arahuetes RM (2013) Beta-N-methylamino-l-alanine causes neurological and pathological phenotypes mimicking Amyotrophic Lateral Sclerosis (ALS): the first step towards an experimental model for sporadic ALS. Environ Toxicol Pharmacol 36(2):243–255

    Article  PubMed  Google Scholar 

  • Murch SJ, Cox PA, Banack SA (2004a) A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam. Proc Natl Acad Sci U S A 101(33):12228–12231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murch SJ, Cox PA, Banack SA, Steele JC, Sacks OW (2004b) Occurrence of beta-methylamino-l-alanine (BMAA) in ALS/PDC patients from Guam. Acta Neurol Scand 110(4):267–269

    Article  CAS  PubMed  Google Scholar 

  • Nielsen PE (1993) Peptide nucleic acid (PNA): a model structure for the primordial genetic material? Orig Life Evol Biosph 23(5–6):323–327

    Article  CAS  PubMed  Google Scholar 

  • Nunn PB, O'Brien P, Pettit LD, Pyburn SI (1989) Complexes of zinc, copper, and nickel with the nonprotein amino acid L-alpha-amino-beta-methylaminopropionic acid: a naturally occurring neurotoxin. J Inorg Biochem 37(2):175–183

    Article  CAS  PubMed  Google Scholar 

  • Okle O, Rath L, Galizia CG, Dietrich DR (2013a) The cyanobacterial neurotoxin beta-N-methylamino-l-alanine (BMAA) induces neuronal and behavioral changes in honeybees. Toxicol Appl Pharmacol 270(1):9–15

    Article  CAS  PubMed  Google Scholar 

  • Okle O, Stemmer K, Deschl U, Dietrich DR (2013b) L-BMAA induced ER stress and enhanced caspase 12 cleavage in human neuroblastoma SH-SY5Y cells at low nonexcitotoxic concentrations. Toxicol Sci 131(1):217–224

    Article  CAS  PubMed  Google Scholar 

  • O'Neal RM, Chen CH, Reynolds CS, Meghal SK, Koeppe RE (1968) The ‘neurotoxicity’ of L-2,4-diaminobutyric acid. Biochem J 106(3):699–706

    Article  PubMed  PubMed Central  Google Scholar 

  • van Onselen R, Cook NA, Phelan RR, Downing TG (2015) Bacteria do not incorporate beta-N-methylamino-L-alanine into their proteins. Toxicon 102:55–61

    Article  PubMed  Google Scholar 

  • Osswald J, Rellan S, Carvalho AP, Gago A, Vasconcelos V (2007) Acute effects of an anatoxin-a producing cyanobacterium on juvenile fish—Cyprinus carpio L. Toxicon 49(5):693–698

    Article  CAS  PubMed  Google Scholar 

  • Pablo J, Banack SA, Cox PA, Johnson TE, Papapetropoulos S, Bradley WG, Buck A, Mash DC (2009) Cyanobacterial neurotoxin BMAA in ALS and Alzheimer’s disease. Acta Neurol Scand 120(4):216–225

    Article  CAS  PubMed  Google Scholar 

  • Paerl HW, Huisman J (2008) Climate. Blooms like it hot. Science 320(5872):57–58

    Article  CAS  PubMed  Google Scholar 

  • Pilbeam D, Bell E (1979) Free amino acids in Crotalaria seeds. Phytochemistry 18:973–985

    Article  CAS  Google Scholar 

  • Ressler C, Redstone PA, Erenberg RH (1961) Isolation and identification of a neuroactive factor from Lathyrus latifolius. Science 134(3473):188–190

    Article  CAS  PubMed  Google Scholar 

  • Reveillon D, Abadie E, Sechet V, Masseret E, Hess P, Amzil Z (2015) Beta-N-methylamino-l-alanine (BMAA) and isomers: distribution in different food web compartments of Thau lagoon, French Mediterranean Sea. Mar Environ Res 110:8–18

    Article  CAS  PubMed  Google Scholar 

  • Rodgers KJ (2014) Non-protein amino acids and neurodegeneration: the enemy within. Exp Neurol 253:192–196

    Article  CAS  PubMed  Google Scholar 

  • Rodgers KJ, Shiozawa N (2008) Misincorporation of amino acid analogues into proteins by biosynthesis. Int J Biochem Cell Biol 40(8):1452–1466

    Article  CAS  PubMed  Google Scholar 

  • Rosen J, Westerberg E, Hellenas KE, Salomonsson ML (2016a) A new method for analysis of underivatized free beta-methylamino-alanine: validation and method comparison. Toxicon 121:105–108

    Article  CAS  PubMed  Google Scholar 

  • Rosen J, Westerberg E, Schmiedt S, Hellenas KE (2016b) BMAA detected as neither free nor protein bound amino acid in blue mussels. Toxicon 109:45–50

    Article  CAS  PubMed  Google Scholar 

  • Roy-Lachapelle A, Solliec M, Sauve S (2015) Determination of BMAA and three alkaloid cyanotoxins in lake water using dansyl chloride derivatization and high-resolution mass spectrometry. Anal Bioanal Chem 407(18):5487–5501

    Article  CAS  PubMed  Google Scholar 

  • Sasaki J, Chijimatsu M, Suzuki K (1998) Taxonomic significance of 2,4-diaminobutyric acid isomers in the cell wall peptidoglycan of actinomycetes and reclassification of Clavibacter toxicus as Rathayibacter toxicus comb. nov. Int J Syst Bacteriol 48(Pt 2):403–410

    Article  CAS  PubMed  Google Scholar 

  • Snyder LR, Cruz-Aguado R, Sadilek M, Galasko D, Shaw CA, Montine TJ (2009a) Lack of cerebral BMAA in human cerebral cortex. Neurology 72(15):1360–1361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Snyder LR, Cruz-Aguado R, Sadilek M, Galasko D, Shaw CA, Montine TJ (2009b) Parkinson-dementia complex and development of a new stable isotope dilution assay for BMAA detection in tissue. Toxicol Appl Pharmacol 240(2):180–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Snyder LR, Hoggard JC, Montine TJ, Synovec RE (2010) Development and application of a comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry method for the analysis of L-beta-methylamino-alanine in human tissue. J Chromatogr A 1217(27):4639–4647. do

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soo RM, Skennerton CT, Sekiguchi Y, Imelfort M, Paech SJ, Dennis PG, Steen JA, Parks DH, Tyson GW, Hugenholtz P (2014) An expanded genomic representation of the phylum cyanobacteria. Genome Biol Evol 6(5):1031–1045

    Article  PubMed  PubMed Central  Google Scholar 

  • Spencer PS, Hugon J, Ludolph A, Nunn PB, Ross SM, Roy DN, Schaumburg HH (1987a) Discovery and partial characterization of primate motor-system toxins. CIBA Found Symp 126:221–238

    CAS  PubMed  Google Scholar 

  • Spencer PS, Ross SM, Nunn PB, Roy DN, Seelig M (1987b) Detection and characterization of plant-derived amino acid motorsystem toxins in mouse CNS cultures. Prog Clin Biol Res 253:349–361

    CAS  PubMed  Google Scholar 

  • Spencer PS, Garner CE, Palmer VS, Kisby GE (2016) Vervets and macaques: similarities and differences in their responses to L-BMAA. Neurotoxicology 56:284–286

    Article  CAS  PubMed  Google Scholar 

  • Vega A, Bell EA, Nunn PB (1968) The preparation of L- and D-alpha-amino- beta-methylaminopropionic acids and the identification of the compound isolated from Cycas circinalis as the L-isomer. Phytochemistry 7:1885–1887

    Article  CAS  Google Scholar 

  • Vyas KJ, Weiss JH (2009) BMAA—an unusual cyanobacterial neurotoxin. Amyotroph Lateral Scler 10(Suppl 2):50–55

    Article  CAS  PubMed  Google Scholar 

  • Walsh CT, O'Brien RV, Khosla C (2013) Nonproteinogenic amino acid building blocks for nonribosomal peptide and hybrid polyketide scaffolds. Angew Chem Int Ed Engl 52(28):7098–7124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weiss JH, Christine CW, Choi DW (1989) Bicarbonate dependence of glutamate receptor activation by beta-N-methylamino-L-alanine: channel recording and study with related compounds. Neuron 3(3):321–326

    Article  CAS  PubMed  Google Scholar 

  • Whiting MG (1962) Toxicity of cycads. Econ Bot 17(4):270–302. doi:10.1007/BF02860136

    Article  Google Scholar 

  • Wonnacott S, Swanson KL, Albuquerque EX, Huby NJ, Thompson P, Gallagher T (1992) Homoanatoxin: a potent analogue of anatoxin-a. Biochem Pharmacol 43(3):419–423

    Article  CAS  PubMed  Google Scholar 

  • Xie X, Basile M, Mash DC (2013) Cerebral uptake and protein incorporation of cyanobacterial toxin beta-N-methylamino-L-alanine. Neuroreport 24(14):779–784

    Article  CAS  PubMed  Google Scholar 

  • Zanchett G, Oliveira-Filho EC (2013) Cyanobacteria and cyanotoxins: from impacts on aquatic ecosystems and human health to anticarcinogenic effects. Toxins (Basel) 5(10):1896–1917

    Article  Google Scholar 

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Rodgers, K.J., Main, B.J. & Samardzic, K. Cyanobacterial Neurotoxins: Their Occurrence and Mechanisms of Toxicity. Neurotox Res 33, 168–177 (2018). https://doi.org/10.1007/s12640-017-9757-2

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