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Review
. 2025 Jul 15:27:e23.
doi: 10.1017/erm.2025.10014.

Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases

Mei Ma  1 , Guangchan Jing  1 , Yue Tian  1 , Ruiying Yin  1 , Mengren Zhang  1
Affiliations
Review

Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases

Mei Ma et al. Expert Rev Mol Med. .

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.

Keywords: AD; DACD; FNDC5; cognitive impairment; irisin.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

Figures

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Graphical abstract
Figure 1.
Figure 1.
Evidence of Irisin’s impact on cognitive impairment.
Figure 2.
Figure 2.
The potential mechanism of Irisin in improving cognitive impairment.
Figure 3.
Figure 3.
Signaling Pathways of Irisin in Improving Cognitive Impairment.
See this image and copyright information in PMC

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