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In vivo Evaluation of a Newly Synthesized Acetylcholinesterase Inhibitor in a Transgenic Drosophila Model of Alzheimer’s Disease

Uras, Giuseppe; Manca, Alessia; Zhang, Pengfei; Markus, Zsuzsa; Mack, Natalie; Allen, Stephanie; Bo, Marco; Xu, Shengtao; Xu, Jinyi; Georgiou, Marios; Zhu, Zheying


Giuseppe Uras

Alessia Manca

Pengfei Zhang

Zsuzsa Markus

Professor of Pharmaceutical Biophysics

Marco Bo

Shengtao Xu

Jinyi Xu

Associate Professor in International Pharmacy and Traditional Medicines


Alzheimer’s disease is a neurodegenerative disease characterized by disrupted memory, learning functions, reduced life expectancy, and locomotor dysfunction, as a result of the accumulation and aggregation of amyloid peptides that cause neuronal damage in neuronal circuits. In the current study, we exploited a transgenic Drosophila melanogaster line, expressing amyloid-β peptides to investigate the efficacy of a newly synthesized acetylcholinesterase inhibitor, named XJP-1, as a potential AD therapy. Behavioral assays and confocal microscopy were used to characterize the drug effect on AD symptomatology and amyloid peptide deposition. The symptomatology induced in this particular transgenic model recapitulates the scenario observed in human AD patients, showing a shortened lifespan and reduced locomotor functions, along with a significant accumulation of amyloid plaques in the brain. XJP-1 treatment resulted in a significant improvement of AD symptoms and a reduction of amyloid plaques by diminishing the amyloid aggregation rate. In comparison with clinically effective AD drugs, our results demonstrated that XJP-1 has similar effects on AD symptomatology, but at 10 times lower drug concentration than donepezil. It also showed an earlier beneficial effect on the reduction of amyloid plaques at 10 days after drug treatment, as observed for donepezil at 20 days, while the other drugs tested have no such effect. As a novel and potent AChE inhibitor, our study demonstrates that inhibition of the enzyme AChE by XJP-1 treatment improves the amyloid-induced symptomatology in Drosophila, by reducing the number of amyloid plaques within the fruit fly CNS. Thus, compound XJP-1 has the therapeutic potential to be further investigated for the treatment of AD.


Uras, G., Manca, A., Zhang, P., Markus, Z., Mack, N., Allen, S., …Zhu, Z. (2021). In vivo Evaluation of a Newly Synthesized Acetylcholinesterase Inhibitor in a Transgenic Drosophila Model of Alzheimer’s Disease. Frontiers in Neuroscience, 15, Article 691222.

Journal Article Type Article
Acceptance Date May 11, 2021
Online Publication Date Jun 30, 2021
Publication Date Jun 30, 2021
Deposit Date May 25, 2021
Publicly Available Date Jul 9, 2021
Journal Frontiers in Neuroscience
Print ISSN 1662-4548
Electronic ISSN 1662-453X
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 15
Article Number 691222
Public URL
Publisher URL


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