Irisin restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis via regulating microglia activation

IntroductionMultiple sclerosis is a chronic autoimmune demyelinating disorder predominantly affecting the white matter of the central nervous system, with experimental autoimmune encephalomyelitis (EAE) serving as its classical animal model. Irisin, a glycosylated protein derived from the proteolyti...

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Main Authors: Qiu-Xia Zhang, Lin-Jie Zhang, Ning Zhao, Li Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1561939/full
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author Qiu-Xia Zhang
Lin-Jie Zhang
Ning Zhao
Li Yang
author_facet Qiu-Xia Zhang
Lin-Jie Zhang
Ning Zhao
Li Yang
author_sort Qiu-Xia Zhang
collection DOAJ
description IntroductionMultiple sclerosis is a chronic autoimmune demyelinating disorder predominantly affecting the white matter of the central nervous system, with experimental autoimmune encephalomyelitis (EAE) serving as its classical animal model. Irisin, a glycosylated protein derived from the proteolytic cleavage of fibronectin type III domain-containing protein 5, plays a significant role in metabolic regulation and inflammatory modulation within the organism.MethodsIn this study, we systematically investigated the therapeutic effects and underlying mechanism of Irisin on EAE and BV2 microglial cells through comprehensive methodologies including quantitative real-time polymerase chain reaction, immunofluorescence staining and western blot.ResultsIrisin exerts neuroprotective effects in EAE mice, significantly ameliorating both clinical and pathological manifestations of the disease. Mechanistically, Irisin attenuated inflammatory response and reduced the number of microglia through NF-κBp65 signaling pathway.ConclusionIn conclusion, these results collectively suggest that Irisin alleviates EAE progression by suppressing microglia activation via the NF-κBp65 pathway, highlighting its potential as a promising therapeutic target for multiple sclerosis treatment.
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publisher Frontiers Media S.A.
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spelling doaj-art-0faa2c2be8e447859cd5a55d5cf964ac2025-08-20T02:29:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15619391561939Irisin restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis via regulating microglia activationQiu-Xia ZhangLin-Jie ZhangNing ZhaoLi YangIntroductionMultiple sclerosis is a chronic autoimmune demyelinating disorder predominantly affecting the white matter of the central nervous system, with experimental autoimmune encephalomyelitis (EAE) serving as its classical animal model. Irisin, a glycosylated protein derived from the proteolytic cleavage of fibronectin type III domain-containing protein 5, plays a significant role in metabolic regulation and inflammatory modulation within the organism.MethodsIn this study, we systematically investigated the therapeutic effects and underlying mechanism of Irisin on EAE and BV2 microglial cells through comprehensive methodologies including quantitative real-time polymerase chain reaction, immunofluorescence staining and western blot.ResultsIrisin exerts neuroprotective effects in EAE mice, significantly ameliorating both clinical and pathological manifestations of the disease. Mechanistically, Irisin attenuated inflammatory response and reduced the number of microglia through NF-κBp65 signaling pathway.ConclusionIn conclusion, these results collectively suggest that Irisin alleviates EAE progression by suppressing microglia activation via the NF-κBp65 pathway, highlighting its potential as a promising therapeutic target for multiple sclerosis treatment.https://www.frontiersin.org/articles/10.3389/fphar.2025.1561939/fullirisinmicrogliaEAEmechanismtherapyneuroinflammation
spellingShingle Qiu-Xia Zhang
Lin-Jie Zhang
Ning Zhao
Li Yang
Irisin restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis via regulating microglia activation
Frontiers in Pharmacology
irisin
microglia
EAE
mechanism
therapy
neuroinflammation
title Irisin restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis via regulating microglia activation
title_full Irisin restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis via regulating microglia activation
title_fullStr Irisin restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis via regulating microglia activation
title_full_unstemmed Irisin restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis via regulating microglia activation
title_short Irisin restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis via regulating microglia activation
title_sort irisin restrains neuroinflammation in mouse experimental autoimmune encephalomyelitis via regulating microglia activation
topic irisin
microglia
EAE
mechanism
therapy
neuroinflammation
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1561939/full
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AT linjiezhang irisinrestrainsneuroinflammationinmouseexperimentalautoimmuneencephalomyelitisviaregulatingmicrogliaactivation
AT ningzhao irisinrestrainsneuroinflammationinmouseexperimentalautoimmuneencephalomyelitisviaregulatingmicrogliaactivation
AT liyang irisinrestrainsneuroinflammationinmouseexperimentalautoimmuneencephalomyelitisviaregulatingmicrogliaactivation