Evidence map›Paper›PMID 39641161›Full record

ArticleDisease models & mechanisms2024

Stat3 mediates Fyn kinase-driven dopaminergic neurodegeneration and microglia activation.

Sahiba Siddiqui, Fang Liu, Anumantha G Kanthasamy, Maura McGrail

Abstract read
In one paragraph

Article in Disease models & mechanisms, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

4 authors.

Sahiba SiddiquiDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Fang LiuDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Anumantha G KanthasamyCenter for Brain Science and Neurodegenerative Diseases, Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA.
Maura McGrailDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.ORCID 0000-0001-9308-6189

Funding

In vivo model of microglia inflammasome signaling in neuroinflammationR24OD020166 · OD · IOWA STATE UNIVERSITY · PI CLARK, KARL J, EKKER, STEPHEN CARL · 2016 to 2023
$7.1M
Conditional genetics and precision genome editing resources for ZebrafishR24OD036201 · OD · IOWA STATE UNIVERSITY · PI KARL J CLARK, Stephen Carl Ekker · 2024 to 2026
$3.0M
Iowa State UniversityNIH HHS R24 OD020166NIH HHS R24 OD020166-05S1NIH HHS R24 OD036201
6 · The paper itself

Abstract

The Alzheimer's disease and Parkinson's disease risk locus FYN kinase is implicated in neurodegeneration and inflammatory signaling. To investigate in vivo mechanisms of Fyn-driven neurodegeneration, we built a zebrafish neural-specific Gal4:UAS model of constitutively active FynY531F signaling. Using in vivo live imaging, we demonstrated that neural FynY531F expression leads to dopaminergic neuron loss and mitochondrial aggregation in 5 day larval brain. Dopaminergic loss coincided with microglia activation and induction of tnfa, il1b and il12a inflammatory cytokine expression. Transcriptome analysis revealed Stat3 signaling as a potential Fyn target. Chemical inhibition experiments confirmed Fyn-driven dopaminergic neuron loss, and the inflammatory response was dependent upon activation of Stat3 and NF-κB pathways. Dual chemical inhibition demonstrated that Stat3 acts synergistically with NF-κB in dopaminergic neuron degeneration. These results identify Stat3 as a novel downstream effector of Fyn signaling in neurodegeneration and inflammation.

Indexed as

Dopaminergic NeuronsMicrogliaNerve DegenerationNF-kappa BProto-Oncogene Proteins c-fynSignal TransductionSTAT3 Transcription FactorZebrafishZebrafish ProteinsAnimalsInflammationMitochondriaNF-kappa BProto-Oncogene Proteins c-fynstat3 protein, zebrafishSTAT3 Transcription FactorZebrafish ProteinsDopaminergic neuronFyn kinaseMicroglia activationMitophagyNF-κBSTAT3TNF-αZebrafish neurodegeneration model

Identifiers

PMID39641161
PMCPMC11646115

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Registered trials

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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.