Role of Netrin-1 Signaling in Nerve Regeneration

• Published in: International journal of molecular sciences 2017-02, Vol.18 (3), p.491-491
• Main Authors: Dun, Xin-Peng, Parkinson, David B
• Format: Article
• Language: English
• Subjects: Animals; Cell Movement; Gene Expression; Humans; Nerve Growth Factors - chemistry; Nerve Growth Factors - metabolism; Nerve Regeneration; Netrin-1; Optic Nerve - physiology; Peripheral Nerve Injuries - genetics; Peripheral Nerve Injuries - metabolism; Peripheral Nerve Injuries - pathology; Protein Binding; Protein Interaction Domains and Motifs; Protein Multimerization; Receptors, Polymeric Immunoglobulin - metabolism; Review; Schwann Cells - metabolism; Signal Transduction; Spinal Cord - metabolism; Spinal Cord Injuries - genetics; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Tumor Suppressor Proteins - chemistry; Tumor Suppressor Proteins - metabolism
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms18030491

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.