Cited by 385Chemokine receptors and signalingNeuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology Research

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Expression of CX 3 CR1 chemokine receptors on neurons and their role in neuronal survival

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Meucci, Olimpia, Fatatis, Alessandro, Simen, Arthur A., Miller, Richard J.·2000·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.090017497PMC PMC16672

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Abstract

Recent in vitro and in vivo studies have shown that the chemokine fractalkine is widely expressed in the brain and localized principally to neurons. Central nervous system expression of CX 3 CR1, the only known receptor for fractalkine, has been demonstrated exclusively on microglia and astrocytes. Thus, it has been proposed that fractalkine regulates cellular communication between neurons (that produce fractalkine) and microglia (that express its receptor). Here we show, for the first time, that hippocampal neurons also express CX 3 CR1. Receptor activation by soluble fractalkine induces activation of the protein kinase Akt, a major component of prosurvival signaling pathways, and nuclear translocation of NF-κB, a downstream effector of Akt. Fractalkine protects hippocampal neurons from the neurotoxicity induced by the HIV-1 envelope protein gp120 IIIB , an effect blocked by anti-CX 3 CR1 antibodies. Experiments with two different inhibitors of the phosphatidylinositol 3-kinase, a key enzyme in the activation of Akt, and with a phospholipid activator of Akt demonstrate that Akt activation is responsible for the neuroprotective effects of fractalkine. These data show that neuronal CX 3 CR1 receptors mediate the neurotrophic effects of fractalkine, suggesting that fractalkine and its receptor are involved in a complex network of both paracrine and autocrine interactions between neurons and glia.

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Authors: Meucci, O., Fatatis, A., Simen, A. A., & Miller, R. J.
Affiliations: University of Chicago (US)
ORCID: Meucci, Olimpia
Fatatis, Alessandro
Simen, Arthur A.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2000-06-27
Volume: 97
Issue: 14
Pages: 8075-8080
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.090017497
PMC: PMC16672
OpenAlex: W2071832924
Cited by: 385
References: 40
Citations by year: 2026: 4 · 2025: 8 · 2024: 12 · 2023: 13 · 2022: 10 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 10 · 2017: 3 · 2016: 13 · 2015: 10 · 2014: 19 · 2013: 12 · 2012: 16
FWCI: 9.42
Type: journal article
Language: en
Update notices: correction (2001-12-18)
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p01ns033826-05, NS33826, NS21442)
U.S. Public Health Service (MC40165)
National Institute on Drug Abuse (R01DA002121, DA-02121)
National Institute of Neurological Disorders and Stroke (P01NS021442, NS-33826)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007009)
Topics: Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: fractalkine, CX3CR1, hippocampal neurons, neuronal survival, neuroprotection, Akt signaling, NF-κB nuclear translocation, phosphatidylinositol 3-kinase, neurotrophic effects, neuron-glia interactions, chemokine receptors
MeSH terms: NF-KappaB Inhibitor alpha, CX3C Chemokine Receptor 1, Animals, Astrocytes, Cell Survival, DNA-Binding Proteins, Hippocampus, Membrane Proteins, Neurons, Phosphatidylinositols, Proto-Oncogene Proteins, Recombinant Proteins, Signal Transduction, Receptors, HIV, NF-kappa B, Protein Serine-Threonine Kinases, Receptors, Cytokine, Chemokines, CXC, Phosphatidylinositol 3-Kinases, Chemokines, CX3C, I-kappa B Proteins, Culture Techniques, Proto-Oncogene Proteins c-akt, Rats, Chemokine CX3CL1

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Expression of CX 3 CR1 chemokine receptors on neurons and their role in neuronal survival

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