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.

Keywords:

• Donepezil hydrochloride
• Alzheimer disease
• Drosophila
• oxidative stress
• molecular docking

Acknowledgements

We are grateful to Council of Scientific and Industrial Research (CSIR), New Delhi, India for the sanction of the research project 37(1721)/19/EMR-II to Dr. Yasir Hasan Siddique. We are also thankful to the Chairman, Department of Zoology, AMU, Aligarh for providing laboratory facilities.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was funded by Council of Scientific and Industrial Research (CSIR), New Delhi, India.