{"title":"New functions of cholinesterases in the development of Alzheimer’s disease as a target for neuroprotective drugs","authors":"G. F. Makhaeva, V. P. Fisenko, S. O. Bachurin","doi":"10.1007/s11172-025-4715-2","DOIUrl":null,"url":null,"abstract":"<div><p>The analysis of the literature indicates a dual role of acetylcholinesterase (AChE) as an enzyme that hydrolyzes the neurotransmitter acetylcholine and simultaneously acts as a “pathological chaperone” promoting β-amyloid oligomerization. The review examines the interaction with AChE of several groups of neuroactive pharmacophore conjugates synthesized in our research group. A set of data obtained using the methods of enzyme kinetics, molecular docking, and fluorescence determination of the competitive displacement of the selective propidium ligand from the peripheral anionic site of AChE is analyzed. The results show the contribution of AChE as a bifunctional target to the neuroprotective potential of new multitarget compounds of various structural classes, allow us to explain the mechanism of the antiaggregatory activity of the conjugates while the original pharmacophores have no this activity, and provide ways to develop new cholinesterase inhibitors with a neuroprotective potential.</p></div>","PeriodicalId":756,"journal":{"name":"Russian Chemical Bulletin","volume":"74 8","pages":"2312 - 2331"},"PeriodicalIF":1.7000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Russian Chemical Bulletin","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s11172-025-4715-2","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
The analysis of the literature indicates a dual role of acetylcholinesterase (AChE) as an enzyme that hydrolyzes the neurotransmitter acetylcholine and simultaneously acts as a “pathological chaperone” promoting β-amyloid oligomerization. The review examines the interaction with AChE of several groups of neuroactive pharmacophore conjugates synthesized in our research group. A set of data obtained using the methods of enzyme kinetics, molecular docking, and fluorescence determination of the competitive displacement of the selective propidium ligand from the peripheral anionic site of AChE is analyzed. The results show the contribution of AChE as a bifunctional target to the neuroprotective potential of new multitarget compounds of various structural classes, allow us to explain the mechanism of the antiaggregatory activity of the conjugates while the original pharmacophores have no this activity, and provide ways to develop new cholinesterase inhibitors with a neuroprotective potential.
期刊介绍：
Publishing nearly 500 original articles a year, by leading Scientists from Russia and throughout the world, Russian Chemical Bulletin is a prominent international journal. The coverage of the journal spans practically all areas of fundamental chemical research and is presented in five sections:
General and Inorganic Chemistry;
Physical Chemistry;
Organic Chemistry;
Organometallic Chemistry;
Chemistry of Natural Compounds and Bioorganic Chemistry.
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