Tuesday, 29 April 2014

CXCR7 another target for remyelination

Williams JL, Patel JR, Daniels BP, Klein RS. Targeting CXCR7/ACKR3 as a therapeutic strategy to promote remyelination in the adult central nervous system. J Exp Med. 2014 Apr. [Epub ahead of print]

Current treatment modalities for the neurodegenerative disease multiple sclerosis (MS) use disease-modifying immunosuppressive compounds but do not promote repair. Although several potential targets that may induce myelin production have been identified, there has yet to be an approved therapy that promotes remyelination in the damaged central nervous system (CNS). Remyelination of damaged axons requires the generation of new oligodendrocytes from oligodendrocyte progenitor cells (OPCs). Although OPCs are detected in MS lesions, repair of myelin is limited, contributing to progressive clinical deterioration. In the CNS, the chemokine CXCL12 promotes remyelination via CXCR4 activation on OPCs, resulting in their differentiation into myelinating oligodendrocytes. Although the CXCL12 scavenging receptor CXCR7/ACKR3 (CXCR7) is also expressed by OPCs, its role in myelin repair in the adult CNS is unknown. 

We show that during cuprizone-induced demyelination, in vivo CXCR7 antagonism augmented OPC proliferation, leading to increased numbers of mature oligodendrocytes within demyelinated lesions. CXCR7-mediated effects on remyelination required CXCR4 activation, as assessed via both phosphorylation specific CXCR4-specific antibodies and administration of CXCR4 antagonists. These findings identify a role for CXCR7 in OPC maturation during remyelination and use a small molecule to therapeutically enhance myelin repair in the demyelinated adult CNS.
So we have an other target for remyelination. This one is a chemokine (a protein that attracts cells) receptor.These findings identify a role for CXCR7 in OPC maturation during remyelination and are the first to use a small molecule to therapeutically enhance myelin repair in the demyelinated adult CNS.

1 comment:

  1. This is what I found on the subject of CXCR7 from 2011.
    http://www.jneuroinflammation.com/content/8/1/170

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