CXCL12/CXCR4/CXCR7 Chemokine Axis in the Central Nervous System: Therapeutic Targets for Remyelination in Demyelinating Diseases

Neuroscientist. 2017 Dec;23(6):627-648. doi: 10.1177/1073858416685690.

Tianci Chu ¹, Lisa B E Shields ², Yi Ping Zhang ², Shi-Qing Feng ³, Christopher B Shields ², Jun Cai ¹ ⁴

Affiliations

1 1 Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USA.
2 2 Norton Neuroscience Institute, Norton Healthcare, Louisville, KY, USA.
3 3 Department of Orthopedics, General Hospital of Tianjin Medical University, Tianjin, People's Republic of China.
4 4 Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, USA.

PMID: 29283028 DOI: 10.1177/1073858416685690

Abstract

The chemokine CXCL12 plays a vital role in regulating the development of the central nervous system (CNS) by binding to its receptors CXCR4 and CXCR7. Recent studies reported that the CXCL12/CXCR4/CXCR7 axis regulates both embryonic and adult oligodendrocyte precursor cells (OPCs) in their proliferation, migration, and differentiation. The changes in the expression and distribution of CXCL12 and its receptors are tightly associated with the pathological process of demyelination in multiple sclerosis (MS), suggesting that modulating the CXCL12/CXCR4/CXCR7 axis may benefit myelin repair by enhancing OPC recruitment and differentiation. This review aims to integrate the current findings of the CXCL12/CXCR4/CXCR7 signaling pathway in the CNS and to highlight its role in oligodendrocyte development and demyelinating diseases. Furthermore, this review provides potential therapeutic strategies for myelin repair by analyzing the relevance between the pathological changes and the regulatory roles of CXCL12/CXCR4/CXCR7 during MS.

Keywords

CXCL12; CXCR; chemokine; myelin; oligodendrocyte; remyelination.

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