Trimethylamine N-oxide (TMAO), in humans, is obtained from gut microbiota and is known to accumulate in human serum as well as cerebrospinal fluid at high levels. There are several reports for the involvement of serum TMAO in various human diseases including, atherosclerosis, neurodegeneration, cancer etc. One important aspect in neurodegeneration is its strong association with memory loss. However, the exact molecular mechanism is not yet explored. Keeping in mind that impairment in memory or onset of Alzheimers is due to decline in cholinergic system of the brain, we thought TMAO could have potentially targeted the cholinergic system. Acetylcholinesterase (AChE) is an important enzyme responsible for the breakdown of neurotransmitter, acetylcholine and therefore plays a crucial role in neuronal plasticity. Recently, our laboratory discovered that TMAO inhibits folding of proteins specifically that are rich in proline content. Since AChE is also a protein characterized by the presence of large number of proline residues, we thought it is worthwhile to investigate if TMAO inhibits its activity. In the present article we investigated the effect of TMAO on the structure and functional activity of AChE. We explored that TMAO is a specific inhibitor of AChE. The results indicate that TMAO might induce decline in the cholinergic system by impairing the function of AChE.
