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.
Authors
- Yuhui Chen (ORCID: https://orcid.org/0009-0006-9347-3481)
- Chengbiao Lu
- Shaomin A Li
- Junli Liu (ORCID: https://orcid.org/0000-0001-8264-2450)
- Sen Zhang (ORCID: https://orcid.org/0000-0003-1409-5795)
- Fan Wang
- Min Cai
- Jianhua Zhao
- Mengke Gao
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Henan Medical University (CN)
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
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Henan Province