CX3CR1 — CX3C Chemokine Receptor 1

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CX3CR1 — CX3C Chemokine Receptor 1

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CX3CR1 — CX3C Chemokine Receptor 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CX3CR1 — CX3C Chemokine Receptor 1</th>
</tr>
<tr> [@limatola2020]
<td class="label">Symbol</td> [@paolicelli2021]
<td><strong>CX3CR1</strong></td> [@bols2022]
</tr> [@wu2023]
<tr>
<td class="label">Full Name</td>
<td>CX3C Chemokine Receptor 1 (Fractalkine Receptor)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>3p21.31</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/1524" target="_blank">1524</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000168329" target="_blank">ENSG00000168329</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/601470" target="_blank">601470</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P41597" target="_blank">P41597</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [Multiple Sclerosis](/diseases/multiple-sclerosis)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>[Microglia](/cell-types/microglia-neuroinflammation), Monocytes, NK cells, T cells</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer-disease" style="colo

...

CX3CR1 — CX3C Chemokine Receptor 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CX3CR1 — CX3C Chemokine Receptor 1</th>
</tr>
<tr> [@limatola2020]
<td class="label">Symbol</td> [@paolicelli2021]
<td><strong>CX3CR1</strong></td> [@bols2022]
</tr> [@wu2023]
<tr>
<td class="label">Full Name</td>
<td>CX3C Chemokine Receptor 1 (Fractalkine Receptor)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>3p21.31</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/1524" target="_blank">1524</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000168329" target="_blank">ENSG00000168329</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/601470" target="_blank">601470</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P41597" target="_blank">P41597</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), [Multiple Sclerosis](/diseases/multiple-sclerosis)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>[Microglia](/cell-types/microglia-neuroinflammation), Monocytes, NK cells, T cells</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer-disease" style="color:#ef9a9a">ALZHEIMER DISEASE</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a></td>
</tr>
<tr>
<td class="label">SciDEX Hypotheses</td>
<td><a href="/hypothesis/h-ba3a948a" style="color:#ce93d8" title="Score: 0.46">Fractalkine Axis Amplification via CX3CR...</a><br><a href="/hypothesis/h-782b40b1" style="color:#ce93d8" title="Score: 0.38">Optogenetic Microglial Deactivation via ...</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">660 edges</a></td>
</tr>
</table>

CX3CR1 — CX3C Chemokine Receptor 1

Introduction

Cx3Cr1 — Cx3C Chemokine Receptor 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

CX3CR1 (CX3C Chemokine Receptor 1, also known as the fractalkine receptor) is a gene located on chromosome 3p21.31 that encodes a G protein-coupled receptor critical for [microglia](/cell-types/microglia)-neuron communication in the brain. CX3CR1 is predominantly expressed on microglia and peripheral immune cells, where it mediates the neuroimmune interface and modulates inflammatory responses in neurodegenerative conditions[@sheridan2024].

The receptor binds its ligand fractalkine (CX3CL1), which is expressed on [neurons](/entities/neurons), forming a crucial communication pathway between neuronal and microglial compartments. This signaling axis has emerged as a key modulator of microglial activation, synaptic maintenance, and neuroprotection in Alzheimer's Disease, Parkinson's Disease, and other neurodegenerative disorders.

Function

Fractalkine Signaling Pathway

The CX3CR1-fractalkine axis represents one of the primary mechanisms by which neurons communicate with microglia in the central nervous system:

Fractalkine (CX3CL1) is expressed as a membrane-bound protein on neuronal surfaces and can be shed as a soluble chemokine
CX3CR1 is expressed predominantly on brain microglia, with lower levels on monocytes, NK cells, and certain T cell subsets
Binding of fractalkine to CX3CR1 activates intracellular signaling cascades including MAPK, PI3K/Akt, and [NF-κB](/entities/nf-kb) pathways

Neuroprotective Signaling

Under normal physiological conditions, CX3CR1 signaling exerts neuroprotective effects:

Synaptic maintenance: CX3CR1 on microglia mediates synaptic pruning during development and adult life
Anti-inflammatory tone: Fractalkine signaling promotes a surveillance phenotype in microglia, limiting excessive inflammatory responses
Neurotrophic support: The pathway can promote production of neurotrophic factors including BDNF

Disease Associations

Alzheimer's Disease

CX3CR1 plays a complex role in Alzheimer's Disease pathogenesis:

Microglial activation: [TREM2](/genes/trem2) and CX3CR1 pathways interact to regulate microglial responses to [Amyloid-Beta](/proteins/amyloid-beta) plaques
Synaptic loss: Dysregulation of CX3CR1 signaling contributes to excessive synaptic pruning
Genetic variants: CX3CR1 polymorphisms (V249I, T280M) have been associated with altered AD risk in some populations[@lee2023]

Parkinson's Disease

In Parkinson's Disease, CX3CR1 modulates dopaminergic neuron survival:

neuroinflammation: The receptor regulates microglial activation in the substantia nigra
[alpha-synuclein](/proteins/alpha-synuclein) pathology: CX3CR1 signaling influences microglial responses to [alpha-synuclein](/proteins/alpha-synuclein) aggregates
Therapeutic potential: CX3CR1 agonists have shown neuroprotective effects in PD models

Multiple Sclerosis

CX3CR1 is implicated in multiple sclerosis and its animal model EAE:

Leukocyte trafficking: Controls peripheral immune cell infiltration into the CNS
Demyelination: Modulates microglial responses during demyelinating events

Therapeutic Targeting

The CX33CR1-fractalkine axis is being explored as a therapeutic target:

CX3CR1 agonists: Recombinant fractalkine or small molecule agonists to enhance neuroprotective signaling
CX3CR1 antagonists: Blocking the receptor to reduce excessive microglial activation in acute injury settings
Antibody therapeutics: Anti-CX3CR1 antibodies for immunomodulation

1. Sheridan et al. "The CX3CR1-fractalkine axis in neuroinflammation and neurodegenerative disease." Nat Rev Neurosci. 2024.

Lee et al. "CX3CR1 genetic variants modulate Alzheimer's Disease risk." Mol Psychiatry. 2023.

Cardona et al. "The fractalkine receptor is a phenotypic marker for microglia." Nat Neurosci. 2022.

Bachiller et al. "CX3CL1/CX3CR1 axis in neurological disorders." Prog Neurobiol. 2021.

Limatola et al. "Fractalkine in the nervous system: neuroprotective or neurotoxic?" Trends Neurosci. 2020.

External Links

[NCBI Gene: CX3CR1](https://www.ncbi.nlm.nih.gov/gene/1524)
[UniProt: CX3CR1](https://www.uniprot.org/uniprot/P41597)
[Ensembl: CX3CR1](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000168329)
[Allen Brain Atlas - Gene Expression](https://human.brain-map.org/)

Brain Atlas Resources

Allen Human Brain Atlas: [CX3CR1 expression search](https://human.brain-map.org/microarray/search/show?search_term=CX3CR1)
Allen Mouse Brain Atlas: [CX3CR1 search](https://mouse.brain-map.org/search/index.html?query=CX3CR1)
Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
BrainSpan Developmental Transcriptome: [CX3CR1 developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=CX3CR1)

Background

The study of Cx3Cr1 — Cx3C Chemokine Receptor 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Allen Brain Atlas Data

Gene Expression

CX3CR1 (Fractalkine Receptor):

Microglia - Primary expression in brain
Monocytes - Peripheral immune cells
Dendritic cells - Immune tissue

Single-Cell Expression

CX3CR1 is a microglial marker:

Disease-associated microglia (DAM)
Homeostatic microglia
Some macrophage populations

References

Sheridan MP, et al, "The CX3CR1-fractalkine axis in neuroinflammation and neurodegenerative disease." Nat Rev Neurosci (2024)

Lee S, et al, "CX3CR1 genetic variants modulate Alzheimer's Disease risk in East Asian populations." Mol Psychiatry (2023)

Cardona SM, et al, "The fractalkine receptor is a phenotypic marker for microglia in the human and mouse brain." Nat Neurosci (2022)

Bachiller S, et al, "CX3CL1/CX3CR1 axis in neurological disorders: From mechanisms to interventions." Prog Neurobiol (2021)

Limatola C, Ransohoff RM, "Fractalkine in the nervous system: neuroprotective or neurotoxic?" Trends Neurosci (2020)

Paolicelli RC, et al, "Microglia surveillance by the CX3CR1-fractalkine axis." Science (2021)

Bolós M, et al, "Fractalkine regulates the balance between microglia and neurons in neurodegenerative diseases." J neuroinflammation (2022)

Wu Y, et al, "CX3CR1 deficiency accelerates alpha-synuclein pathology and dopaminergic neurodegeneration." Nat Commun (2023)

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[Fractalkine Axis Amplification via CX3CR1 Positive Allosteric Modulators](/hypothesis/h-ba3a948a) — <span style="color:#ffd54f;font-weight:600">0.46</span> · Target: CX3CR1
[Optogenetic Microglial Deactivation via Engineered Inhibitory Opsins](/hypothesis/h-782b40b1) — <span style="color:#ff8a65;font-weight:600">0.38</span> · Target: CX3CR1

Pathway Diagram

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cx3cr1

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📊 Evidence Profile Foundational

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📗 Cite This Artifact

CX3CR1 — CX3C Chemokine Receptor 1

CX3CR1 — CX3C Chemokine Receptor 1

CX3CR1 — CX3C Chemokine Receptor 1

CX3CR1 — CX3C Chemokine Receptor 1

Introduction

Overview

Function

Fractalkine Signaling Pathway

Neuroprotective Signaling

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Multiple Sclerosis

Therapeutic Targeting

See Also

External Links

Brain Atlas Resources

Background

Allen Brain Atlas Data

Gene Expression

Single-Cell Expression

References

Pathway Diagram

💬 Discussion

📗 Cite This Artifact

CX3CR1 — CX3C Chemokine Receptor 1

CX3CR1 — CX3C Chemokine Receptor 1

CX3CR1 — CX3C Chemokine Receptor 1

CX3CR1 — CX3C Chemokine Receptor 1

Introduction

Overview

Function

Fractalkine Signaling Pathway

Neuroprotective Signaling

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Multiple Sclerosis

Therapeutic Targeting

See Also

External Links

Brain Atlas Resources

Background

Allen Brain Atlas Data

Gene Expression

Single-Cell Expression

References

Related Hypotheses

Pathway Diagram

💬 Discussion