Evidence map›Paper›PMID 36044549›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Amelioration of pathologic α-synuclein-induced Parkinson's disease by irisin.

Tae-In Kam, Hyejin Park, Shih-Ching Chou, Jonathan G Van Vranken, Melanie J Mittenbühler, Hyeonwoo Kim, Mu A, Yu Ree Choi, Devanik Biswas, Justin Wang and 7 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06893055 (Strength-Endurance Circuit Training in Parkinson's Disease), which is not on this map. Cited by 78 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 2 pooled it
12.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06893055 narecruitingnot on this mapstarted 2025, after this paper: background citation

Strength-Endurance Circuit Training in Parkinson's Disease: Effects on Disease Severity, Physical Performance, Blood Biomarkers and Quality of Life.

TypeinterventionalSponsorGeneral University Hospital, PragueRan2025 to 2027Enrolled90ConditionsParkinson Disease, IdiopathicArmsStrength-Endurance Training, Endurance Training
3 · Its place in the literature

Who cites it

78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Irisin Restrains Oligodendroglial Ferroptosis to Preserve White Matter After Traumatic Brain Injury via AMPK Activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Neurobiology of exercise in Parkinson's disease.Journal of Parkinson's disease · 2026
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 1 country.

Tae-In KamNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.ORCID 0000-0002-7241-4902
Hyejin ParkNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Shih-Ching ChouNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Jonathan G Van VrankenDepartment of Cell Biology, Harvard Medical School, Boston, MA, 02215.
Melanie J MittenbühlerDepartment of Cell Biology, Harvard Medical School, Boston, MA, 02215.
Hyeonwoo KimDepartment of Cell Biology, Harvard Medical School, Boston, MA, 02215.
Mu ADepartment of Cell Biology, Harvard Medical School, Boston, MA, 02215.
Yu Ree ChoiNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Devanik BiswasNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.ORCID 0000-0003-2714-5157
Justin WangNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Yu ShinNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Alexis LoderNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Senthilkumar S KaruppagounderNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Christiane D WrannCardiovascular Research Center, McCance Center for Brain Health, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129.
Valina L DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.ORCID 0000-0002-2915-3970
Bruce M SpiegelmanDepartment of Cell Biology, Harvard Medical School, Boston, MA, 02215.
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.ORCID 0000-0002-6459-0893
Johns Hopkins University · USHarvard University · US

Funding

FNDC5/irisin as a Molecular Mediator of Exercise Benefits in Cognitive FunctionR01NS117694 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Christiane D. Wrann · 2022 to 2026
$2.5M
Elucidating novel molecular mechanisms of irisin-mediated effects via integrinF32DK132864 · NIDDK · DANA-FARBER CANCER INST · PI A, MU · 2022 to 2024
$196k
NIDDK NIH HHS F32 DK132864NINDS NIH HHS R01 NS117694
6 · The paper itself

Abstract

Physical activity provides clinical benefit in Parkinson's disease (PD). Irisin is an exercise-induced polypeptide secreted by skeletal muscle that crosses the blood-brain barrier and mediates certain effects of exercise. Here, we show that irisin prevents pathologic α-synuclein (α-syn)-induced neurodegeneration in the α-syn preformed fibril (PFF) mouse model of sporadic PD. Intravenous delivery of irisin via viral vectors following the stereotaxic intrastriatal injection of α-syn PFF cause a reduction in the formation of pathologic α-syn and prevented the loss of dopamine neurons and lowering of striatal dopamine. Irisin also substantially reduced the α-syn PFF-induced motor deficits as assessed behaviorally by the pole and grip strength test. Recombinant sustained irisin treatment of primary cortical neurons attenuated α-syn PFF toxicity by reducing the formation of phosphorylated serine 129 of α-syn and neuronal cell death. Tandem mass spectrometry and biochemical analysis revealed that irisin reduced pathologic α-syn by enhancing endolysosomal degradation of pathologic α-syn. Our findings highlight the potential for therapeutic disease modification of irisin in PD.

Indexed as

alpha-SynucleinCorpus StriatumFibronectinsParkinson DiseaseAnimalsDisease Models, AnimalDopaminergic NeuronsMicealpha-SynucleinFibronectinsFNDC5 protein, mouseirisinneurodegenerationParkinson’s diseasesynuclein

Identifiers

PMID36044549
PMCPMC9457183
OpenAlexW4293785272

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.