在阿尔茨海默病模型中，OPC吞噬诱导的集簇素可阻止IL-9分泌，从而抑制髓鞘形成。

IF 3.4 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Heliyon Pub Date : 2025-01-03 eCollection Date: 2025-01-15 DOI:10.1016/j.heliyon.2025.e41635

Rebecca M Beiter, Tula P Raghavan, Olivia Suchocki, Hannah E Ennerfelt, Courtney R Rivet-Noor, Andrea R Merchak, Jennifer L Phillips, Tim Bathe, John R Lukens, Stefan Prokop, Jeffrey L Dupree, Alban Gaultier

{"title":"在阿尔茨海默病模型中，OPC吞噬诱导的集簇素可阻止IL-9分泌，从而抑制髓鞘形成。","authors":"Rebecca M Beiter, Tula P Raghavan, Olivia Suchocki, Hannah E Ennerfelt, Courtney R Rivet-Noor, Andrea R Merchak, Jennifer L Phillips, Tim Bathe, John R Lukens, Stefan Prokop, Jeffrey L Dupree, Alban Gaultier","doi":"10.1016/j.heliyon.2025.e41635","DOIUrl":null,"url":null,"abstract":"Background: Variants in the CLUSTERIN gene have been identified as a risk factor for late-onset Alzheimer's disease and are linked to decreased white matter integrity in healthy adults. However, the specific role for clusterin in myelin maintenance in the context of Alzheimer's disease remains unclear.Methods: We employed a combination of immunofluorescence and transmission electron microscopy techniques, primary culture of OPCs, and an animal model of Alzheimer's disease.Results: We found that phagocytosis of debris such as amyloid beta, myelin, and apoptotic cells, increases clusterin expression in oligodendrocyte progenitors. We further discovered that exposure to clusterin inhibits differentiation of oligodendrocyte progenitors. Mechanistically, clusterin blunts production of IL-9 and addition of exogenous IL-9 can rescue clusterin-inhibited myelination. Lastly, we demonstrate that clusterin deletion in mice prevents myelin loss in the 5XFAD model.Discussion: Our data suggest that clusterin could play a key role in Alzheimer's disease myelin pathology.","PeriodicalId":12894,"journal":{"name":"Heliyon","volume":"11 1","pages":"e41635"},"PeriodicalIF":3.4000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761289/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clusterin induced by OPC phagocytosis blocks IL-9 secretion to inhibit myelination in a model of Alzheimer's disease.\",\"authors\":\"Rebecca M Beiter, Tula P Raghavan, Olivia Suchocki, Hannah E Ennerfelt, Courtney R Rivet-Noor, Andrea R Merchak, Jennifer L Phillips, Tim Bathe, John R Lukens, Stefan Prokop, Jeffrey L Dupree, Alban Gaultier\",\"doi\":\"10.1016/j.heliyon.2025.e41635\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: Variants in the CLUSTERIN gene have been identified as a risk factor for late-onset Alzheimer's disease and are linked to decreased white matter integrity in healthy adults. However, the specific role for clusterin in myelin maintenance in the context of Alzheimer's disease remains unclear.Methods: We employed a combination of immunofluorescence and transmission electron microscopy techniques, primary culture of OPCs, and an animal model of Alzheimer's disease.Results: We found that phagocytosis of debris such as amyloid beta, myelin, and apoptotic cells, increases clusterin expression in oligodendrocyte progenitors. We further discovered that exposure to clusterin inhibits differentiation of oligodendrocyte progenitors. Mechanistically, clusterin blunts production of IL-9 and addition of exogenous IL-9 can rescue clusterin-inhibited myelination. Lastly, we demonstrate that clusterin deletion in mice prevents myelin loss in the 5XFAD model.Discussion: Our data suggest that clusterin could play a key role in Alzheimer's disease myelin pathology.\",\"PeriodicalId\":12894,\"journal\":{\"name\":\"Heliyon\",\"volume\":\"11 1\",\"pages\":\"e41635\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-01-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761289/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Heliyon\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1016/j.heliyon.2025.e41635\",\"RegionNum\":3,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/15 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Heliyon","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.heliyon.2025.e41635","RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/15 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

摘要

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Clusterin induced by OPC phagocytosis blocks IL-9 secretion to inhibit myelination in a model of Alzheimer's disease.

Background: Variants in the CLUSTERIN gene have been identified as a risk factor for late-onset Alzheimer's disease and are linked to decreased white matter integrity in healthy adults. However, the specific role for clusterin in myelin maintenance in the context of Alzheimer's disease remains unclear.

Methods: We employed a combination of immunofluorescence and transmission electron microscopy techniques, primary culture of OPCs, and an animal model of Alzheimer's disease.

Results: We found that phagocytosis of debris such as amyloid beta, myelin, and apoptotic cells, increases clusterin expression in oligodendrocyte progenitors. We further discovered that exposure to clusterin inhibits differentiation of oligodendrocyte progenitors. Mechanistically, clusterin blunts production of IL-9 and addition of exogenous IL-9 can rescue clusterin-inhibited myelination. Lastly, we demonstrate that clusterin deletion in mice prevents myelin loss in the 5XFAD model.

Discussion: Our data suggest that clusterin could play a key role in Alzheimer's disease myelin pathology.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Heliyon MULTIDISCIPLINARY SCIENCES-

CiteScore

4.50

自引率

2.50%

发文量

2793

期刊介绍： Heliyon is an all-science, open access journal that is part of the Cell Press family. Any paper reporting scientifically accurate and valuable research, which adheres to accepted ethical and scientific publishing standards, will be considered for publication. Our growing team of dedicated section editors, along with our in-house team, handle your paper and manage the publication process end-to-end, giving your research the editorial support it deserves.