SORLA协调小胶质细胞动力学,增强缺血性中风后的神经保护和恢复。

IF 8.8 2区 医学 Q1 IMMUNOLOGY
Sehui Ma , Tongmei Zhang , Junkai Lv , Shiqi Liang , Shuaizhu Zhao , Xinyue Nan , Ziyue Dou , Jun Yang , Youming Lu , Rong Liu , Hao Li
{"title":"SORLA协调小胶质细胞动力学,增强缺血性中风后的神经保护和恢复。","authors":"Sehui Ma ,&nbsp;Tongmei Zhang ,&nbsp;Junkai Lv ,&nbsp;Shiqi Liang ,&nbsp;Shuaizhu Zhao ,&nbsp;Xinyue Nan ,&nbsp;Ziyue Dou ,&nbsp;Jun Yang ,&nbsp;Youming Lu ,&nbsp;Rong Liu ,&nbsp;Hao Li","doi":"10.1016/j.bbi.2025.05.016","DOIUrl":null,"url":null,"abstract":"<div><div>This study identifies a novel function of Sortilin-related receptor with A-type repeats (SORLA), traditionally linked to Alzheimer’s Disease (AD) as a high-risk gene and associated with neuronal function, in modulating microglial responses to ischemic stroke. We discovered that SORLA expression is significantly reduced in microglia following stroke, a change linked to increased brain injury and diminished neurological recovery. Utilizing SORLA knockout and overexpression models, we demonstrated its essential role in adjusting microglial inflammatory responses. Notably, microglial-specific overexpression of SORLA not only promoted anti-inflammatory actions and effective phagocytosis but also surpassed traditional concepts of microglial polarization. This overexpression mitigated brain damage and enhanced neurofunctional recovery post-stroke, highlighting the neuroprotective potential of SORLA. This breakthrough challenges the prevailing understanding the role of SORLA and opens new therapeutic possibilities for stroke recovery, indicating its wider relevance for neurodegenerative disease management.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 70-86"},"PeriodicalIF":8.8000,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SORLA Orchestrates microglial dynamics for enhanced neuroprotection and recovery following ischemic stroke\",\"authors\":\"Sehui Ma ,&nbsp;Tongmei Zhang ,&nbsp;Junkai Lv ,&nbsp;Shiqi Liang ,&nbsp;Shuaizhu Zhao ,&nbsp;Xinyue Nan ,&nbsp;Ziyue Dou ,&nbsp;Jun Yang ,&nbsp;Youming Lu ,&nbsp;Rong Liu ,&nbsp;Hao Li\",\"doi\":\"10.1016/j.bbi.2025.05.016\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>This study identifies a novel function of Sortilin-related receptor with A-type repeats (SORLA), traditionally linked to Alzheimer’s Disease (AD) as a high-risk gene and associated with neuronal function, in modulating microglial responses to ischemic stroke. We discovered that SORLA expression is significantly reduced in microglia following stroke, a change linked to increased brain injury and diminished neurological recovery. Utilizing SORLA knockout and overexpression models, we demonstrated its essential role in adjusting microglial inflammatory responses. Notably, microglial-specific overexpression of SORLA not only promoted anti-inflammatory actions and effective phagocytosis but also surpassed traditional concepts of microglial polarization. This overexpression mitigated brain damage and enhanced neurofunctional recovery post-stroke, highlighting the neuroprotective potential of SORLA. This breakthrough challenges the prevailing understanding the role of SORLA and opens new therapeutic possibilities for stroke recovery, indicating its wider relevance for neurodegenerative disease management.</div></div>\",\"PeriodicalId\":9199,\"journal\":{\"name\":\"Brain, Behavior, and Immunity\",\"volume\":\"129 \",\"pages\":\"Pages 70-86\"},\"PeriodicalIF\":8.8000,\"publicationDate\":\"2025-05-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain, Behavior, and Immunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S088915912500193X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain, Behavior, and Immunity","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S088915912500193X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

本研究确定了sortilin相关受体a型重复序列(SORLA)的新功能,传统上与阿尔茨海默病(AD)相关,是一种高风险基因,与神经元功能相关,可调节缺血性卒中的小胶质细胞反应。我们发现SORLA在中风后小胶质细胞中的表达显著降低,这一变化与脑损伤增加和神经恢复减弱有关。利用SORLA敲除和过表达模型,我们证明了它在调节小胶质细胞炎症反应中的重要作用。值得注意的是,小胶质细胞特异性过表达SORLA不仅促进了抗炎作用和有效的吞噬作用,而且超越了小胶质细胞极化的传统概念。这种过表达减轻脑损伤,增强脑卒中后的神经功能恢复,突出了SORLA的神经保护潜力。这一突破挑战了对SORLA作用的普遍理解,并为中风恢复开辟了新的治疗可能性,表明其与神经退行性疾病管理的更广泛相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SORLA Orchestrates microglial dynamics for enhanced neuroprotection and recovery following ischemic stroke
This study identifies a novel function of Sortilin-related receptor with A-type repeats (SORLA), traditionally linked to Alzheimer’s Disease (AD) as a high-risk gene and associated with neuronal function, in modulating microglial responses to ischemic stroke. We discovered that SORLA expression is significantly reduced in microglia following stroke, a change linked to increased brain injury and diminished neurological recovery. Utilizing SORLA knockout and overexpression models, we demonstrated its essential role in adjusting microglial inflammatory responses. Notably, microglial-specific overexpression of SORLA not only promoted anti-inflammatory actions and effective phagocytosis but also surpassed traditional concepts of microglial polarization. This overexpression mitigated brain damage and enhanced neurofunctional recovery post-stroke, highlighting the neuroprotective potential of SORLA. This breakthrough challenges the prevailing understanding the role of SORLA and opens new therapeutic possibilities for stroke recovery, indicating its wider relevance for neurodegenerative disease management.
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
CiteScore
29.60
自引率
2.00%
发文量
290
审稿时长
28 days
期刊介绍: Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信