The Effect of Trimethylamine-N-Oxide on Prevention of Protein Aggregation

Overview

As a leading cause of death in the United States, Alzheimer’s Disease affects millions of people each year. Alzheimer’s Disease is a direct result of protein aggregation, which is essentially the buildup of misfolded proteins in the brain, like amyloid-β. Therefore, the purpose of this experiment was to determine the effects of the chemical Trimethylamine-N-oxide (TMAO) and its interaction and prevention of amyloid-β aggregation. Amyloid-β samples were treated with a diluted TMAO solution (concentration 100µM) for one day, and aggregation was measured with a Thioflavin T fluorescence assay. Analysis of the results depict that TMAO had much lower concentrations of amyloid-β (160.4540 RFU) compared to samples that did not have a chemical treatment (191.5957 RFU) and samples treated with curcumin, a chemical that is already known to prohibit aggregation (173.0440 RFU). Additionally, results of a t-test revealed that the data was statistically significant. It is believed that the results were due to the fact that TMAO acts as a molecular crowder, and blocks amyloid-β from folding in the wrong places. In turn, this inhibits aggregation of misfolded amyloid-β. The results of this research may lead to discoveries of potential methods of using TMAO to prevent Alzheimer’s Disease development. Furthermore, understanding the effects of this chemical on protein aggregation can open new doors in research regarding the potential health-related benefits of TMAO.