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The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis.

Overview

Authors: Sina C. Rosenkranz1,2, Joana F. da Rocha1, Luis Moreira1, Pius Schlachter1, Jasmina Bier2, Kaela Healy1, Daniela Neves Silva2, Mohamed Ariff Iqbal1, Marjan Gharagozloo3, Yueyue Xiong4, Matthew A. Murphy4, Helena C. Lichtenfeld2, Lukas Raich2, Michaela Schweizer5, Asude Ertaş1, Marcel S. Woo2, Vanessa Vieira2, Samuel E. Honeycutt6, James P. White6, Gregory A. Wyant1, Manuel A. Friese2, Peter A. Calabresi3, Ruxandra F. Sîrbulescu4,7, Christiane D. Wrann1,8
ORCID iDs: Sina C. Rosenkranz, Joana F. da Rocha, Pius Schlachter, Jasmina Bier, Kaela Healy, Mohamed Ariff Iqbal, Marjan Gharagozloo, Matthew A. Murphy, Helena C. Lichtenfeld, Marcel S. Woo, James P. White, Manuel A. Friese, Peter A. Calabresi, Christiane D. Wrann
  1. Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School,Boston, MA USA
  2. Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf,Hamburg, Germany
  3. Department of Neurology, Johns Hopkins University, School of Medicine,Baltimore, MD USA
  4. Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School,Boston, MA USA
  5. Core Facility Morphology and Electron Microscopy, ZMNH, University Medical Center Hamburg-Eppendorf,Hamburg, Germany
  6. Department of Medicine, Duke University School of Medicine,Durham, NC USA
  7. Department of Neurology, Mass General Brigham, Harvard Medical School,Boston, MA USA
  8. McCance Center for Brain Health, Massachusetts General Hospital,Boston, MA USA
Institutions: Massachusetts General Hospital (United States); University Medical Center Hamburg-Eppendorf (Germany); Johns Hopkins University (United States); Duke University (United States); Mass General Brigham (United States)
Journal: Nature metabolism, volume 8, issue 5, pages 1051-1066
Dates: received 28 November 2024; accepted 30 March 2026; published online 21 May 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s42255-026-01527-7 · PMID 42168599 · PMCID PMC13218937 · OpenAlex W7162009870
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), other condition (population), multiple sclerosis (population), clinical / translational (subfield)
Methods: Statistics, Evoked potentials, fMRI & imaging
Keywords: Diseases of the nervous system, Metabolism
MeSH: Encephalomyelitis, Autoimmune, Experimental*, Fibronectins*, Multiple Sclerosis*, Neuroprotective Agents*, Physical Conditioning, Animal*, Animals, Disease Models, Animal, Female, Mice, Mice, Inbred C57BL, Myokines, Spinal Cord (* major topic)
Topic: Adipose Tissue and Metabolism (Physiology, Medicine), according to OpenAlex
Funding: NINDS (NS117694, NS117598, NS041435); National Institute on Aging (AG062904, AG064580, AG072054, T32AG07057, R56AG056664); Cure Alzheimer’s Fund, Alzheimer Association Research Grant, SPARC Award from the McCance Center for Brain Health, Hassenfeld Clinical Scholar Award, Claflin Distinguished Scholar Award, ADDF-Harrington Scholar Award; Boehringer Ingelheim Fonds travel grant, Advanced Clinician–Scientist Fellowship from the federal ministry of education and research, Germany iSTAR, 01EO2106, the Gemeinnützige Hertie-Stiftung P1200012 and P1250014; MGH Fund for Medical Discovery, grant no. 2024A022508; National MS Society Career transition Grant #TA-2104-37423; Else Kröner Fresenius Foundation
Citations: cited by 1 paper (Europe PMC); 51 references in the paper

Abstract

Aerobic exercise is a disease-modifying intervention in multiple sclerosis (MS) that ameliorates several progressive neurological symptoms in people with MS. Here we show that the exercise hormone irisin mediates neuroprotective effects of exercise in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We demonstrate that voluntary free-wheel running exercise protects against inflammation-induced neurodegeneration in EAE, but these neuroprotective effects are abrogated in mice lacking Fndc5/irisin. Peripheral delivery of irisin increases irisin plasma levels and reduces both clinical symptoms and neuronal loss in EAE. Although peripheral irisin does not alter peripheral and central immune responses in EAE, it induces a direct neuroprotective gene programme in spinal cord neurons and preserves synapses and mitochondrial activity, probably through direct binding to motor neurons. Taken together, these findings suggest that irisin induction in response to exercise confers direct neuroprotective effects in an inflammation-driven neurodegenerative condition, making it an attractive therapeutic candidate for MS.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Code availability

The relevant code is provided in Supplementary Data 6.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data availability

The RNA-seq dataset generated here is available at the Gene Expression Omnibus (GEO) repository under accession number GSE282166 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282166). The following published datasets were used: GSE104899 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE104899), GSE118948 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE118948), GSE194071 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE194071), GSE100329 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100329), GSE279707 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279707), GSE249192 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE249192), and CRA007207 (http://bigd.big.ac.cn/gsa/browse/CRA007207) from the Genome Sequence Archive (GSA). Source data are provided with this paper.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Publisher: n/a → Nature Portfolio

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 24 authors, 2 keywords, 12 MeSH terms, 7 funders, 51 references.

Cite

This paper

Rosenkranz, S. C., da Rocha, J. F., Moreira, L., Schlachter, P., Bier, J., Healy, K., Silva, D. N., Iqbal, M. A., Gharagozloo, M., Xiong, Y., Murphy, M. A., Lichtenfeld, H. C., Raich, L., Schweizer, M., Ertaş, A., Woo, M. S., Vieira, V., Honeycutt, S. E., White, J. P., . . . Wrann, C. D. (2026). The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis. Nature metabolism, 8(5), 1051-1066. https://doi.org/10.1038/s42255-026-01527-7

BibTeX

@article{rosenkranz2026exercise,
author = {Rosenkranz, Sina C. and da Rocha, Joana F. and Moreira, Luis and Schlachter, Pius and Bier, Jasmina and Healy, Kaela and Silva, Daniela Neves and Iqbal, Mohamed Ariff and Gharagozloo, Marjan and Xiong, Yueyue and Murphy, Matthew A. and Lichtenfeld, Helena C. and Raich, Lukas and Schweizer, Michaela and Ertaş, Asude and Woo, Marcel S. and Vieira, Vanessa and Honeycutt, Samuel E. and White, James P. and Wyant, Gregory A. and Friese, Manuel A. and Calabresi, Peter A. and Sîrbulescu, Ruxandra F. and Wrann, Christiane D.},
title = {{The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis}},
journal = {Nature metabolism},
year = {2026},
month = may,
volume = {8},
number = {5},
pages = {1051--1066},
publisher = {Nature Portfolio},
issn = {2522-5812},
doi = {10.1038/s42255-026-01527-7},
url = {https://doi.org/10.1038/s42255-026-01527-7},
pmid = {42168599},
pmcid = {PMC13218937}
}

RIS

TY - JOUR
AU - Rosenkranz, Sina C.
AU - da Rocha, Joana F.
AU - Moreira, Luis
AU - Schlachter, Pius
AU - Bier, Jasmina
AU - Healy, Kaela
AU - Silva, Daniela Neves
AU - Iqbal, Mohamed Ariff
AU - Gharagozloo, Marjan
AU - Xiong, Yueyue
AU - Murphy, Matthew A.
AU - Lichtenfeld, Helena C.
AU - Raich, Lukas
AU - Schweizer, Michaela
AU - Ertaş, Asude
AU - Woo, Marcel S.
AU - Vieira, Vanessa
AU - Honeycutt, Samuel E.
AU - White, James P.
AU - Wyant, Gregory A.
AU - Friese, Manuel A.
AU - Calabresi, Peter A.
AU - Sîrbulescu, Ruxandra F.
AU - Wrann, Christiane D.
TI - The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis
T2 - Nature metabolism
J2 - Nat Metab
PY - 2026
DA - 2026/05/21
VL - 8
IS - 5
SP - 1051
EP - 1066
SN - 2522-5812
PB - Nature Portfolio
DO - 10.1038/s42255-026-01527-7
UR - https://doi.org/10.1038/s42255-026-01527-7
LA - en
ER -

CSL-JSON

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