Title |
The Non-Protein Amino Acid BMAA Is Misincorporated into Human Proteins in Place of l-Serine Causing Protein Misfolding and Aggregation
|
---|---|
Published in |
PLOS ONE, September 2013
|
DOI | 10.1371/journal.pone.0075376 |
Pubmed ID | |
Authors |
Rachael Anne Dunlop, Paul Alan Cox, Sandra Anne Banack, Kenneth John Rodgers |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Australia | 14 | 44% |
United States | 4 | 13% |
New Zealand | 1 | 3% |
Portugal | 1 | 3% |
United Kingdom | 1 | 3% |
Curaçao | 1 | 3% |
Greece | 1 | 3% |
Unknown | 9 | 28% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 22 | 69% |
Scientists | 7 | 22% |
Practitioners (doctors, other healthcare professionals) | 2 | 6% |
Science communicators (journalists, bloggers, editors) | 1 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 5 | 2% |
Australia | 2 | <1% |
United States | 2 | <1% |
South Africa | 1 | <1% |
Sweden | 1 | <1% |
Argentina | 1 | <1% |
Luxembourg | 1 | <1% |
Unknown | 216 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 43 | 19% |
Student > Master | 41 | 18% |
Student > Bachelor | 35 | 15% |
Student > Ph. D. Student | 27 | 12% |
Student > Doctoral Student | 13 | 6% |
Other | 33 | 14% |
Unknown | 37 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 51 | 22% |
Biochemistry, Genetics and Molecular Biology | 45 | 20% |
Chemistry | 23 | 10% |
Medicine and Dentistry | 22 | 10% |
Environmental Science | 13 | 6% |
Other | 30 | 13% |
Unknown | 45 | 20% |