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.
Faculty of Biology, Lomonosov Moscow State University, Leninskie Gory, 1-12, 119991 Moscow, Russia.
Int J Mol Sci. 2023 Nov 16;24(22):16395. doi: 10.3390/ijms242216395.
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, leading to a 7.7-fold increase in catalytic efficiency. The observed non-competitive type of AChE activation by Aβ was associated with increased V and unchanged K. Although BChE activity also increased following incubation with Aβ, this was less efficiently achieved as compared with AChE. Ex vivo electrophysiological experiments showed that 10 μM of Aβ significantly decreased the effect of the AChE inhibitor huperzine A on the synaptic potential parameters.
阿尔茨海默病（AD）发病机制中的一个中心事件是由聚集的淀粉样β（Aβ）肽组成的老年斑的积累。目前用于治疗 AD 的主要药物类别是乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）抑制剂。在这项研究中，已经表明 Aβ在体外增强了 AChE 的活性，在与 10 μM 的 Aβ孵育 48 小时后，达到了 548±5%的最大激活，导致催化效率提高了 7.7 倍。观察到的 Aβ对 AChE 的非竞争性激活与 V 的增加和 K 的不变有关。尽管 BChE 活性在与 Aβ孵育后也增加，但与 AChE 相比，其增加效率较低。离体电生理实验表明，10 μM 的 Aβ显著降低了 AChE 抑制剂石杉碱甲对突触电位参数的影响。
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