title: Role of Netrin-1 Signaling in Nerve Regeneration.
abstract: 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.
authors.affiliation: Peninsula Schools of Medicine and Dentistry, Plymouth University, Plymouth, Devon PL6 8BU, UK. xin-peng.dun@plymouth.ac.uk.|School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, China. xin-peng.dun@plymouth.ac.uk.
authors.forename: Xin-Peng
authors.initials: XP
authors.lastname: Dun
authors.affiliation: Peninsula Schools of Medicine and Dentistry, Plymouth University, Plymouth, Devon PL6 8BU, UK. david.parkinson@plymouth.ac.uk.
authors.forename: David B
authors.initials: DB
authors.lastname: Parkinson
mesh_terms: D000818:Animals; D002465:Cell Movement; D015870:Gene Expression; D006801:Humans; D009414:Nerve Growth Factors / Q000737:chemistry / Q000378:metabolism*; D009416:Nerve Regeneration; D000075388:Netrin-1; D009900:Optic Nerve / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D019056:Receptors, Polymeric Immunoglobulin / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D019056:Receptors, Polymeric Immunoglobulin; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1
keywords: DCC; Neogenin; Netrin-1; Schwann cells; Unc5A–D; bi-functionality; optic nerve; peripheral nerve; regeneration; spinal cord