Advances in the multifunctional roles of CX3CL1 in the central nervous system

C-X3-C motif chemokine ligand 1 (CX3CL1), a structurally unique chemokine in the central nervous system (CNS), shapes physiological and pathological processes via specific binding to its receptor, C-X3-C motif chemokine receptor 1 (CX3CR1). Empirical evidence indicates that this signaling axis exerts dual neuroinflammatory effects: It restrains microglial hyperactivation, yet can promote inflammation under conditions such as chronic stress. Notably, it preserves synaptic plasticity and facilitates remyelination. Age-associated reductions in CX3CL1 exhibit a strong correlation with cognitive decline; administration of exogenous CX3CL1 partially mitigates these deficits. This study provides a comprehensive account of the multifaceted functions and regulatory mechanisms of CX3CL1 in CNS diseases, thereby establishing a basis for potential new therapeutic targets.

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Publication Details

Journal
Frontiers in Aging Neuroscience
Published
2026-01-26
DOI
https://doi.org/10.3389/fnagi.2026.1696689
Primary Topic
Neuroinflammation and Neurodegeneration Mechanisms
Type
article
Field-Weighted Citation Impact
0.00

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article

Advances in the multifunctional roles of CX3CL1 in the central nervous system

Yuhui Chen, Chengbiao Lu, Shaomin A Li, Junli Liu et al.
Frontiers in Aging Neuroscience
Neuroinflammation and Neurodegeneration Mechanisms
article

Advances in the multifunctional roles of CX3CL1 in the central nervous system

Yuhui Chen, Chengbiao Lu, Shaomin A Li, Junli Liu, Sen Zhang, Fan Wang, Min Cai, Jianhua Zhao, Mengke Gao
article en

Abstract

C-X3-C motif chemokine ligand 1 (CX3CL1), a structurally unique chemokine in the central nervous system (CNS), shapes physiological and pathological processes via specific binding to its receptor, C-X3-C motif chemokine receptor 1 (CX3CR1). Empirical evidence indicates that this signaling axis exerts dual neuroinflammatory effects: It restrains microglial hyperactivation, yet can promote inflammation under conditions such as chronic stress. Notably, it preserves synaptic plasticity and facilitates remyelination. Age-associated reductions in CX3CL1 exhibit a strong correlation with cognitive decline; administration of exogenous CX3CL1 partially mitigates these deficits. This study provides a comprehensive account of the multifaceted functions and regulatory mechanisms of CX3CL1 in CNS diseases, thereby establishing a basis for potential new therapeutic targets.

Frontiers in Aging NeuroscienceVol. 18
Brigham and Women's Hospital (US), Harvard University (US), Henan Medical University (CN)
National Natural Science Foundation of China, Natural Science Foundation of Henan Province
Good health and well-being
Openalex Percentile: Top 83%
Neuroinflammation and Neurodegeneration Mechanisms
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