{"title":"The estrogen-brain interface in neuroinflammation: a multidimensional mechanistic insight.","authors":"Jie Lu, Tie-Jun Xian, Cheng-Jun Li, Yang Wang","doi":"10.3389/fnagi.2025.1671552","DOIUrl":null,"url":null,"abstract":"<p><p>Neuroinflammation plays a dual role in the central nervous system, offering protection in acute phases but contributing to chronic damage in neurodegenerative diseases. Estrogen, traditionally recognized for its reproductive functions, exerts extensive neuroprotective effects by modulating neuroinflammatory processes across multiple levels. This review explores the actions of estrogen through its receptors in astrocytes, microglia, and neurons, emphasizing its regulation of signaling pathways such as PI3K/Akt, NF-κB, and WNT/<i>β</i>-catenin. Estrogen also enhances mitochondrial function, promotes DNA repair, and interacts with the gut microbiota to influence systemic inflammation. Furthermore, sex-specific responses to 17<i>α</i>-estradiol highlight the importance of hormonal context. Together, these findings underscore estrogen's potential as a multifaceted modulator of neuroinflammation and provide insight for precision therapeutic strategies.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1671552"},"PeriodicalIF":4.5000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434045/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Aging Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnagi.2025.1671552","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Neuroinflammation plays a dual role in the central nervous system, offering protection in acute phases but contributing to chronic damage in neurodegenerative diseases. Estrogen, traditionally recognized for its reproductive functions, exerts extensive neuroprotective effects by modulating neuroinflammatory processes across multiple levels. This review explores the actions of estrogen through its receptors in astrocytes, microglia, and neurons, emphasizing its regulation of signaling pathways such as PI3K/Akt, NF-κB, and WNT/β-catenin. Estrogen also enhances mitochondrial function, promotes DNA repair, and interacts with the gut microbiota to influence systemic inflammation. Furthermore, sex-specific responses to 17α-estradiol highlight the importance of hormonal context. Together, these findings underscore estrogen's potential as a multifaceted modulator of neuroinflammation and provide insight for precision therapeutic strategies.
期刊介绍：
Frontiers in Aging Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the mechanisms of Central Nervous System aging and age-related neural diseases. Specialty Chief Editor Thomas Wisniewski at the New York University School of Medicine is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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