The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Fractalkine‐induced activation of the phosphatidylinositol‐3 kinase pathway attentuates microglial activation in vivo and in vitro
Abstract
Several neurodegenerative disorders are associated with evidence of inflammation, one feature of which is increased activation of microglia, the most likely cellular source of inflammatory cytokines like interleukin‐1β. It is now recognized that interaction of microglia with other cells contributes to maintenance of microglia in a quiescent state and the complementary distribution of the chemokine, fractalkine (CX 3 CL1) on neurons and its receptor (CX 3 CR1) on microglia, suggests that this interaction may play a role in modulating microglial activation. Here we demonstrate that both soluble and membrane‐bound fractalkine attenuate lipopolysaccharide‐induced microglial activation in vitro. We also show that fractalkine expression is reduced in the brain of aged rats and this is accompanied by an age‐related increase in microglial activation. Treatment of aged rats with fractalkine attenuates the age‐related increase in microglial activation and the evidence indicates that fractalkine‐induced activation of the phosphatidylinositol‐3 kinase pathway is required to maintain microglia in a quiescent state both in vivo and in vitro.
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“The immunosuppressor proteins, including CX3CL1 and CD47 (to control microglial and macrophage function) and CFH (to control T-cell activation and block complement triggers), are already activated by neurodegeneration and block the overproduction of pro-inflammatory signals (such as inducible nitric oxide synthase, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6) [61,62].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [61]
Citations
Cites
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Self-citationA new class of membrane-bound chemokine with a CX3C motif
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Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism
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Control of microglial neurotoxicity by the fractalkine receptor
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Harrison, J. K., Jiang, Y., Chen, S., Xia, Y., Maciejewski, D., McNamara, R. K., Streit, W. J., Salafranca, M. N., Adhikari, S., Thompson, D. A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10896 · Cited by 1,176
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Microglial response to amyloid plaques in APPsw transgenic mice.
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CD200 and membrane protein interactions in the control of myeloid cells
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Expression of CX 3 CR1 chemokine receptors on neurons and their role in neuronal survival
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Items 201–202 of 202
Microglial CX3CR1 signaling mediates stress-induced pain behavior in mice
Fülöp, B., Király, Á., Petrák, R., Müller, J., Biró-Sütő, T., Kormos, V., Tékus, V., Rozmer, K., Dénes, Á., Borbély, É., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1869876
Chemokines in Alzheimer's Disease: Early Defence, Late Damage and the Impact of Sex and Infection
Aldana, B. I., & Freude, K. (2026) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.70273
Metadata
- Authors
- Lyons, A., Lynch, A. M., Downer, E. J., Hanley, R., O’Sullivan, J. B., Smith, A., & Lynch, M. A.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Lynch, Marina A.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2009-08-10
- Volume
- 110
- Issue
- 5
- Pages
- 1547-1556
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2036586619
- Cited by
- 202
- References
- 46
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 16 · 2023: 9 · 2022: 15 · 2021: 12 · 2020: 12 · 2019: 16 · 2018: 11 · 2017: 13 · 2016: 12 · 2015: 5 · 2014: 10 · 2013: 16 · 2012: 11
- FWCI
- 8.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science Foundation Ireland
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- fractalkine, CX3CR1, microglial activation, phosphatidylinositol 3-kinase pathway, neuroinflammation, lipopolysaccharide, aging, neurodegenerative diseases, IL-1β, microglia-neuron interaction
- MeSH terms
- Age Factors, Aging, Animals, Animals, Newborn, Cells, Cultured, Enzyme Activation, Lipopolysaccharides, Male, Membrane Proteins, Solubility, Signal Transduction, Rats, Wistar, Microglia, Phosphatidylinositol 3-Kinases, Rats, Chemokine CX3CL1
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