ArticleNeuron2023
Irisin reduces amyloid-β by inducing the release of neprilysin from astrocytes following downregulation of ERK-STAT3 signaling.
Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Research hotspots of irisin in the nervous system: a bibliometric study and visualization analysis via CiteSpace.Frontiers in aging neuroscience · 2025Pooled it
- Irisin-BDNF axis mediates muscle-brain communication: a complete molecular cascade and potential bidirectional feedback from peripheral activation to central protection.Biogerontology · 2026Review
- The potential and therapeutic advances of the integrin family in neurological disorders.Neural regeneration research · 2026Article
- Microglial Deubiquitinase OTUD7B Stabilizes STAT3 to Promote Neuroinflammation and Cognitive Decline in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A multi-organ spatial metabolomic atlas of exercising mice reveals neuronal Complex I as a convergent and sufficient axis for tau pathology reduction in PS19.bioRxiv : the preprint server for biology · 2026Article
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
- Irisin promotes selective changes in hippocampal mitochondrial metabolism in mice.Biochemistry and biophysics reports · 2026Article
- Muscle-brain crosstalk as a driver of brain health in aging.GeroScience · 2026Review
- Bridging exercise biology and immunometabolism: A novel irisin pathway toward next-generation metabolic and neurodegenerative therapies.Metabolism open · 2026Review
- Network-Level Characterization of Spontaneous Calcium Activity in an In-Vitro Alzheimer's Disease Model.bioRxiv : the preprint server for biology · 2026Article
- Physical Exercise Enhances Melatonin Effect in D-Galactose/Aluminum Chloride-Induced Alzheimer's Disease of Ovariectomized Rats: Irisin Induction Associated with Upregulation of PPAR-γ/IGF-1/BDNF and Decreasing TNF-α/p38-MAPK/NLRP3/GFAP Pathway.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Irisin as an Exerkine of Neuroprotection in Aging and Alzheimer's Disease.Biomolecules · 2026Review
- The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis.Nature metabolism · 2026Article
- The Myokine Irisin Represents an Indirect Pathway Linking Exercise to Hippocampal Subfields Relevant to Alzheimer's Disease and Neurogenesis.Aging cell · 2026Article
- Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells.Nature metabolism · 2026Article
- Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review).International journal of molecular medicine · 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
- FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity.Journal of translational medicine · 2026Article
- Central Irisin Administration Attenuates Hypothalamic TLR4/MyD88-Mediated Neuroinflammatory Signaling in Diet-Induced Obese Mice.Molecular neurobiology · 2026Article
- Exercise-Induced Irisin: A Novel Strategy for Neuroinflammation Alleviation and Neurorepair in Diabetic Retinopathy.International journal of molecular sciences · 2026Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
A pathological hallmark of Alzheimer's disease (AD) is the deposition of amyloid-β (Aβ) protein in the brain. Physical exercise has been shown to reduce Aβ burden in various AD mouse models, but the underlying mechanisms have not been elucidated. Irisin, an exercise-induced hormone, is the secreted form of fibronectin type-III-domain-containing 5 (FNDC5). Here, using a three-dimensional (3D) cell culture model of AD, we show that irisin significantly reduces Aβ pathology by increasing astrocytic release of the Aβ-degrading enzyme neprilysin (NEP). This is mediated by downregulation of ERK-STAT3 signaling. Finally, we show that integrin αV/β5 acts as the irisin receptor on astrocytes required for irisin-induced release of astrocytic NEP, leading to clearance of Aβ. Our findings reveal for the first time a cellular and molecular mechanism by which exercise-induced irisin attenuates Aβ pathology, suggesting a new target pathway for therapies aimed at the prevention and treatment of AD.
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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.