{"title":"多奈哌齐对APP/PS1小鼠阿尔茨海默病不同阶段的疾病改善作用。","authors":"Irina Zueva, Grigory Belyaev, Konstantin Petrov","doi":"10.1007/s11010-025-05310-2","DOIUrl":null,"url":null,"abstract":"<p><p>Despite Alzheimer's disease (AD) representing a significant global health concern, disease-modifying therapeutic options remain elusive. The use of animal models of the disease to develop drugs intended for the treatment of AD does not always predict their efficacy in clinical trials. Our research demonstrates the benefits of a drug-withdrawal approach to screening AD-modifying compounds, focussing on β-amyloid (Aβ)-related pathological changes in APP/PS1 transgenic mice at different stages of the disease. To assess the efficacy of this approach, we examined the AD-modifying effect of donepezil as a reference drug. A significant cognitive decline exhibited by APP/PS1 transgenic mice from 8.4 months of age was accompanied by progressive accumulation of Aβ plaques, decreased synaptophysin and vesicular acetylcholine transporter immunoexpression. Donepezil had a disease-modifying effect, slowing the deterioration of all the pathological markers studied when treatment was started in a pre-symptomatic stage of AD. However, in the group of mice with advanced stage of AD, such disease-modifying effects were not evident.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5123-5139"},"PeriodicalIF":3.7000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Disease-modifying effect of donepezil on APP/PS1 mice at different stages of Alzheimer's disease.\",\"authors\":\"Irina Zueva, Grigory Belyaev, Konstantin Petrov\",\"doi\":\"10.1007/s11010-025-05310-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Despite Alzheimer's disease (AD) representing a significant global health concern, disease-modifying therapeutic options remain elusive. The use of animal models of the disease to develop drugs intended for the treatment of AD does not always predict their efficacy in clinical trials. Our research demonstrates the benefits of a drug-withdrawal approach to screening AD-modifying compounds, focussing on β-amyloid (Aβ)-related pathological changes in APP/PS1 transgenic mice at different stages of the disease. To assess the efficacy of this approach, we examined the AD-modifying effect of donepezil as a reference drug. A significant cognitive decline exhibited by APP/PS1 transgenic mice from 8.4 months of age was accompanied by progressive accumulation of Aβ plaques, decreased synaptophysin and vesicular acetylcholine transporter immunoexpression. Donepezil had a disease-modifying effect, slowing the deterioration of all the pathological markers studied when treatment was started in a pre-symptomatic stage of AD. However, in the group of mice with advanced stage of AD, such disease-modifying effects were not evident.</p>\",\"PeriodicalId\":18724,\"journal\":{\"name\":\"Molecular and Cellular Biochemistry\",\"volume\":\" \",\"pages\":\"5123-5139\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and Cellular Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s11010-025-05310-2\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11010-025-05310-2","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/21 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Disease-modifying effect of donepezil on APP/PS1 mice at different stages of Alzheimer's disease.
Despite Alzheimer's disease (AD) representing a significant global health concern, disease-modifying therapeutic options remain elusive. The use of animal models of the disease to develop drugs intended for the treatment of AD does not always predict their efficacy in clinical trials. Our research demonstrates the benefits of a drug-withdrawal approach to screening AD-modifying compounds, focussing on β-amyloid (Aβ)-related pathological changes in APP/PS1 transgenic mice at different stages of the disease. To assess the efficacy of this approach, we examined the AD-modifying effect of donepezil as a reference drug. A significant cognitive decline exhibited by APP/PS1 transgenic mice from 8.4 months of age was accompanied by progressive accumulation of Aβ plaques, decreased synaptophysin and vesicular acetylcholine transporter immunoexpression. Donepezil had a disease-modifying effect, slowing the deterioration of all the pathological markers studied when treatment was started in a pre-symptomatic stage of AD. However, in the group of mice with advanced stage of AD, such disease-modifying effects were not evident.
期刊介绍：
Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell.
In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
