RESEARCH ARTICLE


Effect of Acetylcholinesterase Inhibitors on the Cognitive Impairments in Transgenic Drosophila Model of Alzheimer’s Disease



Yasir Hasan Siddique1, *, Idrisi Mantasha2, Mohd Shahid2, Smita Jyoti3, Rahul4, Himanshi Varshney1
1 Drosophila Transgenic Laboratory, Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India
2 Department of Chemistry, Faculty of Sciences, Aligarh Muslim University, Aligarh 202002, India
3 Department of Zoology, School of Sciences, IFTM University, Moradabad, Uttar Pradesh, India
4 Department of Zoology, Allahabad University, Prayagraj, Uttar Pradesh, India

Article Information


Identifiers and Pagination:

Year: 2023
Volume: 11
Publisher Id: e187503622305290
DOI: 10.2174/18741967-v11-e230704-2022-8

Article History:

Received Date: 12/12/2022
Revision Received Date: 14/04/2023
Acceptance Date: 05/05/2023
Electronic publication date: 11/07/2023
Collection year: 2023

© 2023 Siddique et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Drosophila Transgenic Laboratory, Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India;
Tel: 0571-2700920-3447; E-mail: yasir_hasansiddique@rediffmail.com


Abstract

Background:

Alzheimer’s disease (AD) is characterized by neuronal loss, synaptic dysfunction, deposition of amyloid-beta (Aβ), and neurofibrillary tangles (NFTs). AD patients exhibit the loss of cholinergic neurons, leads to low levels of acetylcholine and increased activity of acetylcholinesterase which further reduces the levels of acetylcholine. It has now been established that acetylcholine plays a major role in controlling cognitive functions. A number of drugs have been reported to inhibit the activity of acetylcholinesterase, which can improve cognitive dysfunction in AD patients.

Objective:

We have studied the effect of two commonly used acetylcholinesterase inhibitors (Galantamine and Rivastigmine) on the transgenic Drosophila model of AD.

Methods:

The effect of rivastigmine and galantamine was studied on cognitive parameters (Odour choice index, Open field assay, Courtship index and memory loss). Molecular docking was also performed for rivastigmine (with Aβ42 and acetylcholinesterase) and galantamine (with Aβ42 and acetylcholinesterase).

Results:

Both drugs were found to be effective in reducing cognitive defects. However, it was unclear from the data obtained which drug was more effective. The results obtained from the docking studies showed a positive interaction with Aβ42 and acetylcholinesterase for both drugs.

Conclusion:

Rivastigmine and galantamine are potent in reducing cognitive dysfunction in the transgenic AD flies expressing human Aβ42 in the neurons.

Keywords: Alzheimer’s disease, Cognitive impairments, Drosophila, Galantamine, Rivastigmine, Neurons.