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Sep 26, 2013

Imposter Amino Acid Mimics Serine, Kinks Neuroproteins, Prompts Tangling

  • A team of Australian and American scientists have discovered that BMAA, an unusual amino acid produced by cyanobacteria, is able to pose as L-Serine and insinuate itself into proteins, causing them to misfold and aggregate. The scientists speculate that BMAA, which has been detected in the brain tissues of ALS patients, may be rendered less harmful if L-Serine levels are enhanced.

    The scientists, who represent the University of Technology Sydney and the Institute for Ethnomedicine in Jackson Hole, Wyoming, published their findings on September 25 in PLOS ONE, in an article entitled “The non-protein amino acid BMAA is misincorporated into human proteins in place of L-Serine causing protein misfolding and aggregation.”

    Lead author Rachael Dunlop, Ph.D., a cell biologist in Sydney, said, “We found that BMAA inserts itself by seizing the transfer RNA for L-Serine. This, in essence, puts a kink in the protein, causing it to misfold.”

    As the authors note in their study, mechanisms of protein misfolding are of increasing interest in the etiology of neurodegenerative diseases characterized by protein aggregation and tangles. These diseases include ALS, Alzheimer’s disease, and Parkinson’s disease.

    To date, however, research has focused on associating such neurodegenerative illnesses with mutations of genes that control assembly of disease-related proteins. The possibility that environmental factors can trigger abnormal folding in proteins remains relatively unexplored.

    “For many years scientists have linked BMAA to an increased risk of motor neuron disease but the missing pieces of the puzzle relate to how this might occur. Finally, we have one of those pieces,” said Sandra Banack, Ph.D., a researcher at the Institute of Ethnomedicine and co-author of the paper.

    The scientists found that BMAA incorporation into proteins was found to induce apoptosis in neuroblastoma cells in vitro. Even more important, they found that extra L-Serine added to the cell culture can prevent the insertion of BMAA into neuroproteins. The possibility that L-Serine could be used to prevent or slow ALS is now being studied.

    “Even though L-serine occurs in our diet, its safety and efficacy for ALS patients should be properly determined through FDA-approved clinical trials before anyone advocates its use,” said American co-author Dr. Paul Cox.



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