Role of Netrin-1 Signaling in Nerve Regeneration

International Journal of Molecular Sciences

David B. Parkinson¹  Xin-Peng Dun¹ 

[1] Peninsula Schools of Medicine and Dentistry, Plymouth University, Plymouth, Devon PL6 8BU, UK;

关键词: Netrin-1;    DCC;    Neogenin;    Unc5A–D;    bi-functionality;    spinal cord;    optic nerve;    peripheral nerve;    Schwann cells;    regeneration;   

DOI  :  10.3390/ijms18030491

来源: DOAJ

【 摘 要 】

Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A–D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery.

【 授权许可】

Unknown