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Keywords = Beta-N-methylamino-L-alanine

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26 pages, 878 KB  
Review
Airborne Cyanobacterial Toxins and Their Links to Neurodegenerative Diseases
by Zachary James Morris, Elijah W. Stommel and James Spencer Metcalf
Molecules 2025, 30(11), 2320; https://doi.org/10.3390/molecules30112320 - 26 May 2025
Cited by 5 | Viewed by 2916
Abstract
Cyanobacteria can produce a wide range of toxins which have acute and chronic adverse health effects. Affecting a variety of mammalian systems, they are generally characterized according to their mode of action and the organs affected. Cyanobacterial neurotoxins are one cyanotoxin class that [...] Read more.
Cyanobacteria can produce a wide range of toxins which have acute and chronic adverse health effects. Affecting a variety of mammalian systems, they are generally characterized according to their mode of action and the organs affected. Cyanobacterial neurotoxins are one cyanotoxin class that can negatively affect human health, and representatives of other cyanotoxins classes are increasingly showing neurotoxic effects. Of the various human exposure routes to cyanobacterial toxins, the significance of the airborne and inhalation route requires much greater clarity and understanding. People may be exposed to mixtures of cyanobacterial neurotoxins through the inhalation of sprays and dust, along with the potential to directly enter the central nervous system when crossing the blood-brain barrier. This review aims to summarize the current state of knowledge concerning airborne cyanobacterial neurotoxins, research gaps, health effects, and the need for management practices to protect human and animal health. Full article
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10 pages, 1677 KB  
Communication
Use of a Mixed Cationic-Reverse Phase Column for Analyzing Small Highly Polar Metabolic Markers in Biological Fluids for Multiclass LC-HRMS Method
by Marco Roverso, Iole Maria Di Gangi, Gabriella Favaro, Paolo Pastore and Sara Bogialli
Appl. Sci. 2020, 10(20), 7137; https://doi.org/10.3390/app10207137 - 14 Oct 2020
Cited by 2 | Viewed by 2603
Abstract
The determination of small highly polar metabolites at low concentrations is challenging when reverse-phase (RP) chromatography is used for multiclass analysis. A mixed cationic-RP column coupled to high-resolution tandem MS (HR-MS/MS) was tested for highly polar compounds in biological fluids, i.e., trimethylamine N-oxide [...] Read more.
The determination of small highly polar metabolites at low concentrations is challenging when reverse-phase (RP) chromatography is used for multiclass analysis. A mixed cationic-RP column coupled to high-resolution tandem MS (HR-MS/MS) was tested for highly polar compounds in biological fluids, i.e., trimethylamine N-oxide (TMAO) and the isobaric molecules beta-methylamino-L-alanine (BMAA) and 2,4-diaminobutyric acid (DAB). The efficient retention and separation of the above compounds were obtained with common and MS-friendly RP conditions, reaching high selectivity and sensitivity. The method was firstly assessed in plasma and urine, showing good linearity in the range 50–1000 µg/L and 500–10,000 µg/L for TMAO and both BMAA and DAB, respectively. Excellent precision (RDS < 3%) and good accuracies (71–85%) were observed except for BMAA in plasma, whose experimental conditions should be specifically optimized. Preliminary tests performed on compounds with biological relevance and a wider range of polarities proved the effectiveness of this chromatographic solution, allowing the simultaneous analysis of a larger panel of metabolites, from very small and polar compounds, like trimethylamine, to quite lipophilic molecules, such as corticosterone. The proposed LC-HRMS protocol is an excellent alternative to hydrophilic interaction liquid chromatography and ion-pairing RP chromatography, thus providing another friendly analytical tool for metabolomics. Full article
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27 pages, 1728 KB  
Article
The First Proteomic Study of Nostoc sp. PCC 7120 Exposed to Cyanotoxin BMAA under Nitrogen Starvation
by Olga A. Koksharova, Ivan O. Butenko, Olga V. Pobeguts, Nina A. Safronova and Vadim M. Govorun
Toxins 2020, 12(5), 310; https://doi.org/10.3390/toxins12050310 - 9 May 2020
Cited by 18 | Viewed by 6284
Abstract
The oldest prokaryotic photoautotrophic organisms, cyanobacteria, produce many different metabolites. Among them is the water-soluble neurotoxic non-protein amino acid beta-N-methylamino-L-alanine (BMAA), whose biological functions in cyanobacterial metabolism are of fundamental scientific and practical interest. An early BMAA inhibitory effect on nitrogen fixation and [...] Read more.
The oldest prokaryotic photoautotrophic organisms, cyanobacteria, produce many different metabolites. Among them is the water-soluble neurotoxic non-protein amino acid beta-N-methylamino-L-alanine (BMAA), whose biological functions in cyanobacterial metabolism are of fundamental scientific and practical interest. An early BMAA inhibitory effect on nitrogen fixation and heterocyst differentiation was shown in strains of diazotrophic cyanobacteria Nostoc sp. PCC 7120, Nostoc punctiforme PCC 73102 (ATCC 29133), and Nostoc sp. strain 8963 under conditions of nitrogen starvation. Herein, we present a comprehensive proteomic study of Nostoc (also called Anabaena) sp. PCC 7120 in the heterocyst formation stage affecting by BMAA treatment under nitrogen starvation conditions. BMAA disturbs proteins involved in nitrogen and carbon metabolic pathways, which are tightly co-regulated in cyanobacteria cells. The presented evidence shows that exogenous BMAA affects a key nitrogen regulatory protein, PII (GlnB), and some of its protein partners, as well as glutamyl-tRNA synthetase gltX and other proteins that are involved in protein synthesis, heterocyst differentiation, and nitrogen metabolism. By taking into account the important regulatory role of PII, it becomes clear that BMAA has a severe negative impact on the carbon and nitrogen metabolism of starving Nostoc sp. PCC 7120 cells. BMAA disturbs carbon fixation and the carbon dioxide concentrating mechanism, photosynthesis, and amino acid metabolism. Stress response proteins and DNA repair enzymes are upregulated in the presence of BMAA, clearly indicating severe intracellular stress. This is the first proteomic study of the effects of BMAA on diazotrophic starving cyanobacteria cells, allowing a deeper insight into the regulation of the intracellular metabolism of cyanobacteria by this non-protein amino acid. Full article
(This article belongs to the Special Issue Biological Role of Cyanotoxins: Experimental and In-Field Evidence)
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27 pages, 1154 KB  
Article
Beta-N-Methylamino-l-Alanine: LC-MS/MS Optimization, Screening of Cyanobacterial Strains and Occurrence in Shellfish from Thau, a French Mediterranean Lagoon
by Damien Réveillon, Eric Abadie, Véronique Séchet, Luc Brient, Véronique Savar, Michèle Bardouil, Philipp Hess and Zouher Amzil
Mar. Drugs 2014, 12(11), 5441-5467; https://doi.org/10.3390/md12115441 - 17 Nov 2014
Cited by 61 | Viewed by 9910
Abstract
β-N-methylamino-l-alanine (BMAA) is a neurotoxic non-protein amino acid suggested to be involved in neurodegenerative diseases. It was reported to be produced by cyanobacteria, but also found in edible aquatic organisms, thus raising concern of a widespread human exposure. However, the chemical [...] Read more.
β-N-methylamino-l-alanine (BMAA) is a neurotoxic non-protein amino acid suggested to be involved in neurodegenerative diseases. It was reported to be produced by cyanobacteria, but also found in edible aquatic organisms, thus raising concern of a widespread human exposure. However, the chemical analysis of BMAA and its isomers are controversial, mainly due to the lack of selectivity of the analytical methods. Using factorial design, we have optimized the chromatographic separation of underivatized analogues by a hydrophilic interaction chromatography coupled to tandem mass spectrometry (HILIC-MS/MS) method. A combination of an effective solid phase extraction (SPE) clean-up, appropriate chromatographic resolution and the use of specific mass spectral transitions allowed for the development of a highly selective and sensitive analytical procedure to identify and quantify BMAA and its isomers (in both free and total form) in cyanobacteria and mollusk matrices (LOQ of 0.225 and 0.15 µg/g dry weight, respectively). Ten species of cyanobacteria (six are reported to be BMAA producers) were screened with this method, and neither free nor bound BMAA could be found, while both free and bound DAB were present in almost all samples. Mussels and oysters collected in 2009 in the Thau Lagoon, France, were also screened, and bound BMAA and its two isomers, DAB and AEG, were observed in all samples (from 0.6 to 14.4 µg/g DW), while only several samples contained quantifiable free BMAA. Full article
(This article belongs to the Special Issue Emerging Marine Toxins)
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14 pages, 170 KB  
Review
The Cyanobacteria Derived Toxin Beta-N-Methylamino-L-Alanine and Amyotrophic Lateral Sclerosis
by Sandra A. Banack, Tracie A. Caller and Elijah W. Stommel
Toxins 2010, 2(12), 2837-2850; https://doi.org/10.3390/toxins2122837 - 20 Dec 2010
Cited by 95 | Viewed by 13726
Abstract
There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis). The non-protein amino acid beta-N-methylamino-L-alanine (BMAA) was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex [...] Read more.
There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis). The non-protein amino acid beta-N-methylamino-L-alanine (BMAA) was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam, and has been implicated as a potential environmental factor in ALS, Alzheimer’s disease, and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-protein amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. The ramifications of discovering an environmental trigger for ALS are enormous. In this article, we discuss the history, ecology, pharmacology and clinical ramifications of this ubiquitous, cyanobacteria-derived toxin. Full article
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