Li-Pao Fang, Ching-Hsin Lin, Yasser Medlej, Renping Zhao, Hsin-Fang Chang, Qilin Guo, Zhonghao Wu, Yixun Su, Na Zhao, Davide Gobbo, Amanda Wyatt, Vanessa Wahl, Frederic Fiore, Szu-Min Tu, Ulrich Boehm, Wenhui Huang, Shan Bian, Amit Agarwal, Marcel A. Lauterbach, Chenju Yi, Jianqin Niu, Anja Scheller, Frank Kirchhoff, Xianshu Bai
{"title":"Oligodendrocyte precursor cells facilitate neuronal lysosome release","authors":"Li-Pao Fang, Ching-Hsin Lin, Yasser Medlej, Renping Zhao, Hsin-Fang Chang, Qilin Guo, Zhonghao Wu, Yixun Su, Na Zhao, Davide Gobbo, Amanda Wyatt, Vanessa Wahl, Frederic Fiore, Szu-Min Tu, Ulrich Boehm, Wenhui Huang, Shan Bian, Amit Agarwal, Marcel A. Lauterbach, Chenju Yi, Jianqin Niu, Anja Scheller, Frank Kirchhoff, Xianshu Bai","doi":"10.1038/s41467-025-56484-8","DOIUrl":null,"url":null,"abstract":"<p>Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes. A reduction in the number or branching of OPCs reduces these contacts, which is associated with lysosome accumulation and altered metabolism in neurons and more senescent neurons with age. A similar reduction in OPC branching and neuronal lysosome accumulation is seen in an early-stage mouse model of Alzheimer’s disease. Our findings have implications for the prevention of age-related pathologies and the treatment of neurodegenerative diseases.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"40 1","pages":""},"PeriodicalIF":15.7000,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-56484-8","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes. A reduction in the number or branching of OPCs reduces these contacts, which is associated with lysosome accumulation and altered metabolism in neurons and more senescent neurons with age. A similar reduction in OPC branching and neuronal lysosome accumulation is seen in an early-stage mouse model of Alzheimer’s disease. Our findings have implications for the prevention of age-related pathologies and the treatment of neurodegenerative diseases.
期刊介绍：
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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