US EPA

7418936 

Journal Article 

The non-protein amino acid BMAA is misincorporated into human proteins in place of L-serine causing protein misfolding and aggregation 

Dunlop, RA; Cox, PA; Banack, SA; Rodgers, KJ; , 

2013 

1 

PLoS ONE
EISSN: 1932-6203 

PUBLIC LIBRARY SCIENCE 

SAN FRANCISCO 

8 

9 

e75376 

English 

24086518 

10.1371/journal.pone.0075376 

WOS:000325218700082 

https://dx.plos.org/10.1371/journal.pone.0075376
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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 tRNA(Ala) 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. 

2 amino 3 methylaminopropionic acid; cell protein; serine; amino acid metabolism; amino acid substitution; article; controlled study; human; human cell; protein aggregation; protein folding; protein modification; protein synthesis; Amino Acids, Diamino; Cell Culture Techniques; Cell Line; Chromatography, High Pressure Liquid; Cyanobacteria; Human Umbilical Vein Endothelial Cells; Humans; L-Lactate Dehydrogenase; Nerve Tissue Proteins; Proteostasis Deficiencies; Tandem Mass Spectrometry; Tritium