modulation of activity of acetylcholinesterase with polyoxovolframs

Abstract

Introduction: Alzheimer's disease has its pathoanatomical origin. The loss of synapses and neurons is dominant in this disease and it leads to changes, primarily at the acetylcholine neurotransmitter system. Polyoxometalates (POM) are highly potent and selective inhibitors of acetylcholinesterase, the enzyme responsible for the disintegration of acetylcholine, and therefore they find their usage in the treatment of Alzheimer's disease, since it would increase and extend the effect of the missing acetylcholine. The aim: Presenting the results of in vitro influence of POM on the activity of AChE. Material and methods:In our study we have tested the effects of five Heteropolyoxovolframs: Results:The tested compounds make the inhibition of AChE activity in a dose-dependent manner. Inhibition parameters obtained in this study demonstrate that the compounds 2, 3 and 5 are very potent inhibitors of the enzyme activity. On the other hand, compounds 1 and 4 demonstrate about a hundred, or a thousand times, less potent inhibitory effect on the activity of AchE, compering to the most potent inhibitor (compound 3), whose IC50 value is 4,79×10 -7 mol/L. The results obtained in this study are consistent with previously demonstrated inhibitory effect of polyoxovolframs on cholinesterase activity. Conclusion: According to the obtained results we can conclude that the tested Polyoxometalates at physiological pH values inhibit the activity of AChE, and that the inhibition is dose-dependent. Inhibitory range of tested POM in this study verify significantly, possibly as a result of differences in charge, size and shape of these POM.