Effect of donepezil hydrochloride on the transgenic Drosophila expressing human Aβ-42.

Abstract

Aim: In the present study, the effect of donepezil hydrochloride was studied on the transgenic Drosophila expressing human amyloid beta-42 in the neurons.

Methods: Donepezil hydrochloride at final concentration of 0.1, 1 and 10 mM was mixed in the diet and the flies expressing human amyloid beta-42 under Upstream Activation Sequence control (Alzheimer Disease [AD] flies) were allowed to feed on it for 30 days.

Results: The AD flies exposed to various doses of Donepezil hydrochloride showed a dose dependent significant delay in the loss of climbing ability, increase in activity, reduction in the oxidative stress and apoptotic markers. A significant improvement was also observed in cognitive parameters. A dose dependent significant reduction in the activity of acetylcholinesterase was also observed. The docking studies suggest the positive interaction between donepezil, amyloid beta-42 and acetylcholinesterase. The results obtained from immunohistochemistry also showed a dose dependent significant reduction in the amyloid beta-42 aggregates.

Conclusion: The results suggest that donepezil hydrochloride is potent enough to reduce the AD symptoms being mimicked in transgenic flies.