Abstract
There is a strong body of evidence linking the non-protein amino acid (NPAA) β-methylamino-l-alanine (BMAA) to the development of a number of neurodegenerative diseases. BMAA has been found globally, is produced by a number of organisms including cyanobacteria, diatoms, and dinoflagellates; and has been shown to biomagnify through trophic levels. The role of BMAA in neurodegenerative disease is highlighted by its presence in the brains of a number of neurodegenerative disease patients, where it was found in a protein-bound form. We have previously shown that BMAA is bound to cell proteins, and results in the upregulation of the unfolded protein response, an endoplasmic reticulum stress response activated by the presence of misfolded proteins within the cell. Structurally aberrant proteins are features of a number of neurodegenerative diseases, and further investigation of how BMAA interacts with proteins is crucial to our understanding of its toxicity. Here we use radiolabelled BMAA to investigate the interaction and binding of BMAA to eukaryotic and prokaryotic proteins. We found differences in the presence and distribution of protein-bound BMAA between E. coli and neuroblastoma cells, with an increase in binding over time only seen in the eukaryotic cells. We also found that BMAA was unable to bind to pure proteins, or cell lysate in native or denaturing conditions, indicating that biological processing is required for BMAA to bind to proteins.
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Funding was from the Motor Neurone Disease Research Institute of Australia (Grant-in-aid); this research is supported by an Australian Government Research Training Program Scholarship.
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All experiments were conducted or supervised by BM, CI and KR; manuscript text was written by BM and KR.
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This manuscript represents original research, and has not been published in part or in whole elsewhere. This publication is not currently being considered for publication elsewhere. All authors have actively been involved in work leading to this manuscript, and have read and agreed with its publication. This article does not contain any studies with human participants or animals performed by any of the authors.
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Main, B.J., Italiano, C.J. & Rodgers, K.J. Investigation of the interaction of β-methylamino-l-alanine with eukaryotic and prokaryotic proteins. Amino Acids 50, 397–407 (2018). https://doi.org/10.1007/s00726-017-2525-z
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DOI: https://doi.org/10.1007/s00726-017-2525-z