論文 - 詳細
| RRC ID | 83918 |
|---|---|
| 著者 | Siddiqui S, Liu F, Kanthasamy AG, McGrail M. |
| タイトル | Stat3 mediates Fyn kinase-driven dopaminergic neurodegeneration and microglia activation. |
| ジャーナル | Dis Model Mech |
| 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. |
| 巻・号 | 17(12) |
| 公開日 | 2024-12-1 |
| DOI | 10.1242/dmm.052011 |
| PII | 363349 |
| PMID | 39641161 |
| PMC | PMC11646115 |
| MeSH | Animals Dopaminergic Neurons* / metabolism Dopaminergic Neurons* / pathology Inflammation / pathology Microglia* / metabolism Microglia* / pathology Mitochondria / metabolism NF-kappa B* / metabolism Nerve Degeneration* / pathology Proto-Oncogene Proteins c-fyn* / genetics Proto-Oncogene Proteins c-fyn* / metabolism STAT3 Transcription Factor* / metabolism Signal Transduction* Zebrafish* Zebrafish Proteins* / genetics Zebrafish Proteins* / metabolism |
| IF | 4.651 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | Tg(huC:GVP) |