Evidence map›Paper›PMID 35172141›Full record

ArticleCell reports2022

Interleukin-6 triggers toxic neuronal iron sequestration in response to pathological α-synuclein.

Jacob K Sterling, Tae-In Kam, Samyuktha Guttha, Hyejin Park, Bailey Baumann, Amir A Mehrabani-Tabari, Hannah Schultz, Brandon Anderson, Ahab Alnemri, Shih-Ching Chou and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.6field-weighted citation impact, top 3% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
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  3. Sex-dependent impact ofGenes & diseases · 2026
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  19. IL-6 Does Not Influence the Expression ofInternational journal of molecular sciences · 2024
    Article
  20. Review
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

14 authors at 2 institutions in 1 country.

Jacob K SterlingScheie Eye Institute, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Medical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Tae-In KamNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Diana Helis Henry and Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA.
Samyuktha GutthaScheie Eye Institute, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Hyejin ParkNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Bailey BaumannScheie Eye Institute, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Medical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Amir A Mehrabani-TabariNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hannah SchultzScheie Eye Institute, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Brandon AndersonScheie Eye Institute, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Ahab AlnemriScheie Eye Institute, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Shih-Ching ChouNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Juan C TroncosoDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Valina L DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Diana Helis Henry and Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA.
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Diana Helis Henry and Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA. Electronic address: tdawson@jhmi.edu.
Joshua L DunaiefScheie Eye Institute, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: jdunaief@pennmedicine.upenn.edu.
Johns Hopkins University · USPenn Presbyterian Medical Center · US

Funding

Understanding Mechanisms of a-synuclein pathologyP50NS038377 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DAWSON, TED M. · 1998 to 2019
$38.8M
Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI MARILYN S. ALBERT · 2020 to 2026
$29.3M
Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
Region-Specific Vulnerability of the Lewy Body Dementia's BrainR01NS123456 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KAM, TAE-IN, KANG, SUNG UNG · 2021 to 2025
$3.6M
The IL-6 Induced Retinal Iron Sequestration ResponseR01EY028916 · NEI · UNIVERSITY OF PENNSYLVANIA · PI DUNAIEF, JOSHUA L · 2019 to 2023
$2.4M
IL-1Beta-Induced Retinal Iron Accumulation in Age-Related Macular DegenerationF30EY032339 · NEI · UNIVERSITY OF PENNSYLVANIA · PI STERLING, JACOB KHAN · 2021 to 2023
$121k
NEI NIH HHS F30 EY032339NEI NIH HHS P30 EY001583NEI NIH HHS R01 EY028916NIA NIH HHS P30 AG066507NINDS NIH HHS P50 NS038377NINDS NIH HHS R01 NS123456
6 · The paper itself

Abstract

α-synuclein (α-syn) aggregation and accumulation drive neurodegeneration in Parkinson's disease (PD). The substantia nigra of patients with PD contains excess iron, yet the underlying mechanism accounting for this iron accumulation is unclear. Here, we show that misfolded α-syn activates microglia, which release interleukin 6 (IL-6). IL-6, via its trans-signaling pathway, induces changes in the neuronal iron transcriptome that promote ferrous iron uptake and decrease cellular iron export via a pathway we term the cellular iron sequestration response, or CISR. The brains of patients with PD exhibit molecular signatures of the IL-6-mediated CISR. Genetic deletion of IL-6, or treatment with the iron chelator deferiprone, reduces pathological α-syn toxicity in a mouse model of sporadic PD. These data suggest that IL-6-induced CISR leads to toxic neuronal iron accumulation, contributing to synuclein-induced neurodegeneration.

Indexed as

alpha-SynucleinAnimalsBehavior, AnimalDisease Models, AnimalDopaminergic NeuronsFemaleInterleukin-6IronIron Chelating AgentsMaleMiceMice, Inbred C57BLMice, TransgenicNerve DegenerationNeuronsParkinson Diseasealpha-SynucleinInterleukin-6IronIron Chelating Agentscellular iron sequestration responseinterleukin 6ironmicroglianeurodegenerationneuroinflammationParkinson's diseaseα-synuclein

Identifiers

PMID35172141
PMCPMC8898592
OpenAlexW4213038617

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.