Alzheimer’s Disease Drugs- In Vitro Comparison of Cholinesterase Inhibition and beta-amyloid Modulation

Author(s): Ondrej Holas, Jan Korabecny, Zuzana Gazova, Katarina Siposova, Kamil Musilek, Veronika Opletalova, Lukas Gorecki, Eugenie Nepovimova, Katarina Spilovska, Eva Mezeiova, Kamil Kuca*

Journal Name: Letters in Drug Design & Discovery

Volume 14 , Issue 6 , 2017

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Graphical Abstract:


Background: Alzheimer’s disease is progressive neurodegenerative disease incidence of which has been steadily growing for past decades. Etiology of Alzheimer’s disease consists of multiple micro and macroscopic changes and to this day is not satisfactorily understood. Conventional therapy is based on inhibition of acetylcholinesterase of Alzheimer’s disease is connected with considerable worldwide expenses.

Objective: Six clinically used cholinesterase inhibitors (donepezil, physostigmine, galanthamine, huperzine A, rivastigmine and tacrine) and memantine were compared according to their cholinesterase inhibitory properties. Additionally, the ability of tested compounds to directly inhibit protein aggregation as well as the capability to promote the protein amyloid fibrils depolymerization was determined.

Method: Adopted colorimetric assay according to Ellman was used to evaluate the inhibition aktivity against cholinesterases. The ability of compounds to influence agregation inhibition and depolymerization activity was measured by means of thioflavin fluorescence assay.

Results: Huperzine A was found to be the most potent, highly selective acetylcholinesterase inhibitor. Tacrine and physostigmine were the most potent butyrylcholinesterase inhibitors. Several inhibitors showed some weak potency to affect protein fibrils aggregation or depolymerization. Namely rivastigmine and galanthamine showed some effect on protein polymerization and depolymerization.

Conclusion: Data provided by experiments suggest that clinically used and standard cholinesterase inhibitors influence the protein superstructures however the effect is weak. The need for novel structures of cholinesterase inhibitors with sufficient protein aggregation inhibition and/or depolymerization is evident.

Keywords: Alzheimer’s disease, acetylcholinesterase, inhibitors, amyloid, in vitro, drugs.

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Article Details

Year: 2017
Page: [743 - 750]
Pages: 8
DOI: 10.2174/1570180814666161228143846
Price: $65

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