ArticleJournal of neuroinflammation2012
The gamma chain subunit of Fc receptors is required for alpha-synuclein-induced pro-inflammatory signaling in microglia.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review.Frontiers in aging neuroscience · 2022Pooled it
- Integrated In Vivo and In Vitro Analysis of Alpha-Synuclein Aggregation and Neuroinflammatory Amplification in a Composite Parkinson's Disease Model.Neurochemical research · 2026Article
- Retinal Architecture in Parkinson's Disease with Rapid Eye Movement Sleep Behaviour Disorder: Insights from a Scoping Review.Annals of neurosciences · 2026Review
- Prebiotic intervention changes host and microbe proteomes in plasma extracellular vesicles of Parkinson's disease.Scientific reports · 2026Article
- Formulation and Evaluation of Astaxanthin-Loaded Invasomes as Therapeutic Approaches for Alzheimer's Disease Induced in Rats: Role of SIRT-1/BDNF/miRNA-134/GSK-3β Signaling.Molecular neurobiology · 2025Article
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Alpha-synuclein expression in neurons modulates Japanese encephalitis virus infection.Journal of virology · 2024Article
- Alpha-Synuclein and Microglia in Parkinson's Disease: From Pathogenesis to Therapeutic Prospects.Journal of clinical medicine · 2024Review
- Novel microglial transcriptional signatures promote social and cognitive deficits following repeated social defeat.Communications biology · 2024Article
- Causal role of myeloid cells in Parkinson's disease: Mendelian randomization study.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Neuroinflammatory gene expression profiles of reactive glia in the substantia nigra suggest a multidimensional immune response to alpha synuclein inclusions.Neurobiology of disease · 2024Article
- Characterization of covalent inhibitors that disrupt the interaction between the tandem SH2 domains of SYK and FCER1G phospho-ITAM.PloS one · 2024Article
- Alpha-Synuclein Contribution to Neuronal and Glial Damage in Parkinson's Disease.International journal of molecular sciences · 2023Review
- Clinical biomarkers for Lewy body diseases.Cell & bioscience · 2023Review
- Phosphodiesterase-4 Inhibition in Parkinson's Disease: Molecular Insights and Therapeutic Potential.Cellular and molecular neurobiology · 2023Review
- Characterization of covalent inhibitors that disrupt the interaction between the tandem SH2 domains of SYK and FCER1G phospho-ITAM.bioRxiv : the preprint server for biology · 2023Article
- Sex and Age Differences in a Progressive Synucleinopathy Mouse Model.Biomolecules · 2023Article
- Microglia and Astrocytes Dysfunction and Key Neuroinflammation-Based Biomarkers in Parkinson's Disease.Brain sciences · 2023Review
- A functional role for alpha-synuclein in neuroimmune responses.Journal of neuroimmunology · 2023Review
- Association of Glial Activation and α-Synuclein Pathology in Parkinson's Disease.Neuroscience bulletin · 2023Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe protein alpha-synuclein (α-SYN), which is found in the Lewy bodies of dopamine-producing (DA) neurons in the substantia nigra (SN), has an important role in the pathogenesis of Parkinson's disease (PD). Previous studies have shown that neuroinflammation plays a key role in PD pathogenesis. In an AAV-synuclein mouse model of PD, we have found that over-abundance of α-SYN triggers the expression of NF-κB p65, and leads to microglial activation and DA neurodegeneration. We also have observed that Fcγ receptors (FcγR), proteins present on the surface of microglia that bind immunoglobulin G (IgG) and other ligands, are key modulators of α-SYN-induced neurodegeneration.
methodsIn order to study the role of FcγRs in the interactions of α-SYN and microglia, we treated the primary microglial cultures from wild-type (WT) and FcγR-/- mice with aggregated human α-SYN in vitro.
resultsUsing immunocytochemistry, we found that α-SYN was taken up by both WT and FcγR-/- microglia, however, their patterns of internalization were different, with aggregation in autophagosomes in WT cells and more diffuse localization in FcγR-/- microglia. In WT microglia, α-SYN induced the nuclear accumulation of NF-κB p65 protein and downstream chemokine expression while in FcγR-/- mouse microglia, α-SYN failed to trigger the enhancement of nuclear NF-κB p65, and the pro-inflammatory signaling was reduced.
conclusionsOur results suggest that α-SYN can interact directly with microglia and can be internalized and trafficked to autophagosomes. FcγRs mediate this interaction, and in the absence of the gamma chain, there is altered intracellular trafficking and attenuation of pro-inflammatory NF-κB signaling. Therefore, blocking either FcγR signaling or downstream NF-κB activation may be viable therapeutic strategies 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.