ArticleMolecular cell2023
Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90α.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 55 citations in OpenAlex.
- Epigenetic insights of Olympic champions: nuclear and mitochondrial DNA methylation and regulators of aging.GeroScience · 2026Article
- Irisin upregulation as a contributory mechanism for the therapeutic benefits of SGLT-2 inhibitors.Pharmacology & therapeutics · 2026Review
- Exercise and Fat: A Primer.Sports medicine - open · 2026Review
- Irisin maintains ER homeostasis and activates AMPK via integrin αVβ5 to attenuate CSE + LPS-induced emphysema and inflammation.Respiratory research · 2026Article
- Host HSP90AA1 Contributes to Lactobacillus Johnsonii Adhesion and Reduced Pathogen Adhesion in Bovine Vaginal Epithelial Cells.Probiotics and antimicrobial proteins · 2026Article
- Plasma Proteomic Signatures of Physical Activity Provide Insights into Biological Impacts and its Protective Role against Dementia.Medicine and science in sports and exercise · 2026Observational
- FNDC5 deficiency alters placental development, maternal body weight, and fetal-placental growth in mice.Scientific reports · 2026Article
- Irisin as an Exerkine of Neuroprotection in Aging and Alzheimer's Disease.Biomolecules · 2026Review
- In Silico Analyses Suggest That Exercise-Induced Irisin-Mediated Neuroprotection Supports Non-Pharmacological Preventive Strategies for Alzheimer's Disease in Public Health.International journal of environmental research and public health · 2026Article
- Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells.Nature metabolism · 2026Article
- Irisin as a Regulator of Brain Energy Homeostasis: Implications for Age-Related Neurodegenerative Diseases.Cells · 2026Review
- FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity.Journal of translational medicine · 2026Article
- Seven days of warm-water immersion enhances resting irisin and BDNF, but not klotho, in older men.Experimental physiology · 2026Article
- Exercise-Induced Irisin: A Novel Strategy for Neuroinflammation Alleviation and Neurorepair in Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Recombinant Irisin Therapy Alters Brain Transcriptome and Protects Against Ischemic Damage in Middle-Aged Rats.Stroke · 2026Article
- Skeletal Muscle as an Auto-, Para- and Endocrine Organ: The Role of Myokines in Muscle Metabolism and Other Metabolic Organs.Physiological research · 2025Review
- Developing Subcutaneous Formulations for Irisin as a Potential Therapeutic.Pharmaceutical research · 2025Article
- Therapeutic Potential of Irisin in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Critical Role of the Endothelial αV/β5 Integrin Receptor Signaling Pathway in Promoting Irisin-induced Hippocampal BDNF Expression.Molecular neurobiology · 2025Article
- Electrical Stimulation-Induced Muscle Damage Alters Hippocampal BDNF Signaling.The European journal of neuroscience · 2025Article
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22 authors at 4 institutions in 1 country.
Funding
Abstract
Exercise benefits the human body in many ways. Irisin is secreted by muscle, increased with exercise, and conveys physiological benefits, including improved cognition and resistance to neurodegeneration. Irisin acts via αV integrins; however, a mechanistic understanding of how small polypeptides like irisin can signal through integrins is poorly understood. Using mass spectrometry and cryo-EM, we demonstrate that the extracellular heat shock protein 90α (eHsp90α) is secreted by muscle with exercise and activates integrin αVβ5. This allows for high-affinity irisin binding and signaling through an Hsp90α/αV/β5 complex. By including hydrogen/deuterium exchange data, we generate and experimentally validate a 2.98 Å RMSD irisin/αVβ5 complex docking model. Irisin binds very tightly to an alternative interface on αVβ5 distinct from that used by known ligands. These data elucidate a non-canonical mechanism by which a small polypeptide hormone like irisin can function through an integrin receptor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.