Can Activation of Acetylcholinesterase by β-Amyloid Peptide Decrease the Effectiveness of Cholinesterase Inhibitors?

Irina V Zueva; Elmira A Vasilieva; Gulnara A Gaynanova; Andrey V Moiseenko; Anna D Burtseva; Konstantin M Boyko; Lucia Ya Zakharova; Konstantin A Petrov

doi:10.3390/ijms242216395

Can Activation of Acetylcholinesterase by β-Amyloid Peptide Decrease the Effectiveness of Cholinesterase Inhibitors?

Int J Mol Sci. 2023 Nov 16;24(22):16395. doi: 10.3390/ijms242216395.

Authors

Irina V Zueva¹, Elmira A Vasilieva¹, Gulnara A Gaynanova¹, Andrey V Moiseenko², Anna D Burtseva^{3

4}, Konstantin M Boyko³, Lucia Ya Zakharova¹, Konstantin A Petrov^{1

5}

Affiliations

¹ Arbuzov Institute of Organic and Physical Chemistry, Federal Research Center "Kazan Scientific Center of the Russian Academy of Sciences", Arbuzov Str., 8, 420088 Kazan, Russia.
² Faculty of Biology, Lomonosov Moscow State University, Leninskie Gory, 1-12, 119991 Moscow, Russia.
³ Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Prospect, 33/2, 119071 Moscow, Russia.
⁴ Landau Phystech School of Physics and Research, Moscow Institute of Physics and Technology, Institutsky Lane, 9, Dolgoprudny, 141700 Moscow, Russia.
⁵ Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya Str., 420008 Kazan, Russia.

Abstract

A central event in the pathogenesis of Alzheimer's disease (AD) is the accumulation of senile plaques composed of aggregated amyloid-β (Aβ) peptides. The main class of drugs currently used for the treatment of AD are the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. In this study, it has been shown that Aβ augmented AChE activity in vitro, maximum activation of 548 ± 5% was achieved following 48 h of incubation with 10 μM of Aβ_1-40, leading to a 7.7-fold increase in catalytic efficiency. The observed non-competitive type of AChE activation by Aβ_1-40 was associated with increased V_max and unchanged K_m. Although BChE activity also increased following incubation with Aβ_1-40, this was less efficiently achieved as compared with AChE. Ex vivo electrophysiological experiments showed that 10 μM of Aβ_1-40 significantly decreased the effect of the AChE inhibitor huperzine A on the synaptic potential parameters.

Keywords: cholinesterase; non-essential enzyme activators; β-amyloid peptide.

MeSH terms

Acetylcholinesterase
Alzheimer Disease* / drug therapy
Alzheimer Disease* / pathology
Amyloid beta-Peptides
Butyrylcholinesterase
Cholinesterase Inhibitors* / pharmacology
Cholinesterase Inhibitors* / therapeutic use
Humans

Substances

Cholinesterase Inhibitors
Acetylcholinesterase
Amyloid beta-Peptides
Butyrylcholinesterase

Grants and funding

19-15-00344-П/Russian Science Foundation