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 , Tongmei Zhang , Junkai Lv , Shiqi Liang , Shuaizhu Zhao , Xinyue Nan , Ziyue Dou , Jun Yang , Youming Lu , Rong Liu , 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 , Tongmei Zhang , Junkai Lv , Shiqi Liang , Shuaizhu Zhao , Xinyue Nan , Ziyue Dou , Jun Yang , Youming Lu , Rong Liu , 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}
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.
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.