Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases

Abstract Introduction Irisin is a glycosylated polypeptide hormone derived from muscles that plays a crucial role in learning and memory by promoting the growth of hippocampal neurons, thereby influencing cognitive function. Objective Despite increasing evidence, a comprehensive understanding of...

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Main Authors: Mei Ma, Guangchan Jing, Yue Tian, Ruiying Yin, Mengren Zhang
Format: Article
Language:English
Published: Cambridge University Press 2025-01-01
Series:Expert Reviews in Molecular Medicine
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Online Access:https://www.cambridge.org/core/product/identifier/S1462399425100148/type/journal_article
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author Mei Ma
Guangchan Jing
Yue Tian
Ruiying Yin
Mengren Zhang
author_facet Mei Ma
Guangchan Jing
Yue Tian
Ruiying Yin
Mengren Zhang
author_sort Mei Ma
collection DOAJ
description Abstract Introduction Irisin is a glycosylated polypeptide hormone derived from muscles that plays a crucial role in learning and memory by promoting the growth of hippocampal neurons, thereby influencing cognitive function. Objective Despite increasing evidence, a comprehensive understanding of the exact role of irisin remains elusive, necessitating further research to unravel the complex mechanisms through which irisin influences cognitive function and to explore therapeutic approaches targeting irisin. Method A literature review was performed by searching PubMed for articles published between 2012 and 2024, using the keywords ‘fibronectin type III domain-containing 5 (FNDC5)’, ‘irisin’, ‘cognitive impairment’, ‘Alzheimer’s disease’, ‘Age-related cognitive dysfunction’ and ‘Diabetes-associated cognitive dysfunction’, combined with Boolean operators (AND/OR). Results This review highlighted the potential impact of irisin on cognitive function in the context of ageing, diabetes and Alzheimer’s disease. The anti-cognitive impairment effects of irisin are associated with the regulation of energy metabolism, insulin resistance, inflammation, oxidative stress, amyloid-beta deposition, synaptogenesis and plasticity. The signalling pathways through which irisin improves cognitive impairment are complex and highly regulated processes, involving multiple signalling pathways such as the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway, mitogen-activated protein kinase (MAPK) signalling pathway, nuclear factor-κB (NF-κB) signalling pathway, ERK-STAT3 signalling pathway, cAMP/PKA/CREB signalling pathway and Nrf2/HO-1 signalling pathway. Conclusion This review delves into the positive effects of irisin on cognitive impairment, examines the signalling pathways related to fibronectin type III domain-containing 5 (FNDC5)/irisin and provides future perspectives for research on the anti-cognitive impairment effects of irisin.
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spelling doaj-art-9d0bdcdb26de42989ed4e3a3f44bb0b52025-08-20T12:57:29ZengCambridge University PressExpert Reviews in Molecular Medicine1462-39942025-01-012710.1017/erm.2025.10014Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related DiseasesMei Ma0Guangchan Jing1Yue Tian2Ruiying Yin3Mengren Zhang4https://orcid.org/0009-0006-5174-1994Department of Traditional Chinese Medicine, https://ror.org/04jztag35Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Traditional Chinese Medicine, https://ror.org/04jztag35Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Traditional Chinese Medicine, https://ror.org/04jztag35Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Traditional Chinese Medicine, https://ror.org/04jztag35Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Traditional Chinese Medicine, https://ror.org/04jztag35Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China Abstract Introduction Irisin is a glycosylated polypeptide hormone derived from muscles that plays a crucial role in learning and memory by promoting the growth of hippocampal neurons, thereby influencing cognitive function. Objective Despite increasing evidence, a comprehensive understanding of the exact role of irisin remains elusive, necessitating further research to unravel the complex mechanisms through which irisin influences cognitive function and to explore therapeutic approaches targeting irisin. Method A literature review was performed by searching PubMed for articles published between 2012 and 2024, using the keywords ‘fibronectin type III domain-containing 5 (FNDC5)’, ‘irisin’, ‘cognitive impairment’, ‘Alzheimer’s disease’, ‘Age-related cognitive dysfunction’ and ‘Diabetes-associated cognitive dysfunction’, combined with Boolean operators (AND/OR). Results This review highlighted the potential impact of irisin on cognitive function in the context of ageing, diabetes and Alzheimer’s disease. The anti-cognitive impairment effects of irisin are associated with the regulation of energy metabolism, insulin resistance, inflammation, oxidative stress, amyloid-beta deposition, synaptogenesis and plasticity. The signalling pathways through which irisin improves cognitive impairment are complex and highly regulated processes, involving multiple signalling pathways such as the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway, mitogen-activated protein kinase (MAPK) signalling pathway, nuclear factor-κB (NF-κB) signalling pathway, ERK-STAT3 signalling pathway, cAMP/PKA/CREB signalling pathway and Nrf2/HO-1 signalling pathway. Conclusion This review delves into the positive effects of irisin on cognitive impairment, examines the signalling pathways related to fibronectin type III domain-containing 5 (FNDC5)/irisin and provides future perspectives for research on the anti-cognitive impairment effects of irisin. https://www.cambridge.org/core/product/identifier/S1462399425100148/type/journal_articleADcognitive impairmentDACDFNDC5irisin
spellingShingle Mei Ma
Guangchan Jing
Yue Tian
Ruiying Yin
Mengren Zhang
Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases
Expert Reviews in Molecular Medicine
AD
cognitive impairment
DACD
FNDC5
irisin
title Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases
title_full Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases
title_fullStr Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases
title_full_unstemmed Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases
title_short Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases
title_sort irisin emerging therapeutic targets for cognitive impairment related diseases
topic AD
cognitive impairment
DACD
FNDC5
irisin
url https://www.cambridge.org/core/product/identifier/S1462399425100148/type/journal_article
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AT guangchanjing irisinemergingtherapeutictargetsforcognitiveimpairmentrelateddiseases
AT yuetian irisinemergingtherapeutictargetsforcognitiveimpairmentrelateddiseases
AT ruiyingyin irisinemergingtherapeutictargetsforcognitiveimpairmentrelateddiseases
AT mengrenzhang irisinemergingtherapeutictargetsforcognitiveimpairmentrelateddiseases