ArticleThe Journal of experimental medicine2019
Fyn kinase regulates misfolded α-synuclein uptake and NLRP3 inflammasome activation in microglia.
Article in The Journal of experimental medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
145 citing papers in PubMed, 2 syntheses or guidelines pooled it, 241 citations in OpenAlex.
- Neuroprotective Effects of Resveratrol in In vivo and In vitro Experimental Models of Parkinson's Disease: a Systematic Review.Neurotoxicity research · 2022Pooled it
- Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review.Frontiers in aging neuroscience · 2022Pooled it
- Fyn kinase: a key mechanistic regulator and therapeutic target in tauopathy and neurodegenerative diseases.Translational neurodegeneration · 2026Review
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Protein Kinase C-delta (PKCδ) in Neurodegeneration and Cerebral Ischemia: Molecular Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- [Regulatory mechanisms of post-translational modifications in inflammasome signaling: a review].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Article
- Current review on inducible nitric oxide synthase and Src tyrosine kinase inhibitors as disease-modifiers in preclinical models of epilepsy.Histology and histopathology · 2026Review
- Icaritin ameliorates MPTP-induced Parkinson's disease model by targeting the NLRP3 inflammasome pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- Review
- Microglial Innate Immune Memory: Implications and Research Advances in Central Nervous System Disorders.Current issues in molecular biology · 2026Review
- Plant natural products targeting NLRP3 inflammasome in Parkinson's disease: Molecular activation and regulation to therapeutics.iScience · 2026Review
- Inflammasomes in glioblastoma.Journal of neuroinflammation · 2026Review
- ATP13A2 restrains macrophage NLRP3 inflammasome activation to repress neurodegeneration via modulating mitochondrial homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Clinically advanced NLRP3 inhibitor modulates microglial transcriptome and alleviates α-synuclein-induced progression of parkinsonism.Journal of neuroinflammation · 2026Article
- Microglia, Astrocytes, and Oligodendrocytes in Parkinson's Disease: Neuroinflammatory Crosstalk and Emerging Therapeutic Strategies.Biomolecules · 2026Review
- Organelle stress in NLRP3 inflammasome: a central mediator of neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Microglia heterogeneity and therapeutic strategies in Parkinson's disease.Frontiers in immunology · 2026Review
- Age-related nigral downregulation of the Parkinson's risk factor FAM49B primes human microglia for inflammaging.npj aging · 2025Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
Persistent microglia-mediated neuroinflammation is a major pathophysiological contributor to the progression of Parkinson's disease (PD), but the cell-signaling mechanisms governing chronic neuroinflammation are not well understood. Here, we show that Fyn kinase, in conjunction with the class B scavenger receptor CD36, regulates the microglial uptake of aggregated human α-synuclein (αSyn), which is the major component of PD-associated Lewy bodies. αSyn can effectively mediate LPS-independent priming and activation of the microglial NLRP3 inflammasome. Fyn kinase regulates both of these processes; it mediates PKCδ-dependent NF-κB-p65 nuclear translocation, leading to inflammasome priming, and facilitates αSyn import into microglia, contributing to the generation of mitochondrial reactive oxygen species and consequently to inflammasome activation. In vivo experiments using A53T and viral-αSyn overexpression mouse models as well as human PD neuropathological results further confirm the role of Fyn in NLRP3 inflammasome activation. Collectively, our study identifies a novel Fyn-mediated signaling mechanism that amplifies neuroinflammation in PD.
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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.