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Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes: in vitro ERK1/2 activation and role in Alzheimer’s disease
Abstract
Inflammatory mediators have been implicated in the pathophysiology of neurodegenerative diseases. Here we report the presence of the chemokine receptor CXCR3 and its ligand, IP-10, in normal and Alzheimer's disease (AD) brains. CXCR3 was detected constitutively on neurons and neuronal processes in various cortical and subcortical regions; IP-10 was observed in a subpopulation of astrocytes in normal brain, and was markedly elevated in astrocytes in AD brains. Many IP-10(+) astrocytes were associated with senile plaques and had an apparently coordinated upregulation of MIP-1beta. Moreover, we showed that CXCR3 ligands, IP-10 and Mig, were able to activate ERK1/2 pathway in mouse cortical neurons, suggesting a novel mechanism of neuronal-glial interaction.
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“were found to be elevated in patients with AD and associated with neurological deficits (57–60).”
From Deletion of Abi3 gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis (2021) · cites this paper as [59]
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Metadata
- Authors
- Xia, M. Q., Bacskai, B. J., Knowles, R. B., Qin, S. X., & Hyman, B. T.
- Affiliations
- Harvard University (US)
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2000-08
- Volume
- 108
- Issue
- 1-2
- Pages
- 227-235
- ISSN
- 0165-5728 (ISSN-L)
- OpenAlex
- W2002670780
- Cited by
- 269
- References
- 55
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 15 · 2023: 16 · 2022: 14 · 2021: 13 · 2020: 8 · 2019: 10 · 2018: 10 · 2017: 13 · 2016: 3 · 2015: 4 · 2014: 11 · 2013: 13 · 2012: 4
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroimmunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P50 AG05134, P50AG005134)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- CXCR3, CXCL10, CCL22, MIP-1β, Alzheimer's disease, reactive astrocytes, neurons, ERK1/2 activation, neuron-glia interactions, amyloid plaques, chemokines, neuroinflammation, cortical neurons
- MeSH terms
- Aged, Alzheimer Disease, Animals, Astrocytes, Cells, Cultured, Cerebral Cortex, Enzyme Activation, Female, Glial Fibrillary Acidic Protein, Humans, Ligands, Neurons, Phosphorylation, Up-Regulation, Macrophage Inflammatory Proteins, Receptors, Chemokine, Chemokines, CXC, Gene Expression Profiling, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Intercellular Signaling Peptides and Proteins, Mice, Chemokine CXCL10, Receptors, CXCR3, Chemokine CXCL9, Chemokine CCL4, Plaque, Amyloid
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