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Int. J. Mol. Sci. 2017, 18(3), 491; doi:10.3390/ijms18030491

Role of Netrin-1 Signaling in Nerve Regeneration

1
Peninsula Schools of Medicine and Dentistry, Plymouth University, Plymouth, Devon PL6 8BU, UK
2
School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, China
*
Author to whom correspondence should be addressed.
Academic Editor: Xiaofeng Jia
Received: 14 December 2016 / Revised: 20 February 2017 / Accepted: 22 February 2017 / Published: 24 February 2017
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside)
View Full-Text   |   Download PDF [4655 KB, uploaded 24 February 2017]   |  

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. View Full-Text
Keywords: Netrin-1; DCC; Neogenin; Unc5A–D; bi-functionality; spinal cord; optic nerve; peripheral nerve; Schwann cells; regeneration Netrin-1; DCC; Neogenin; Unc5A–D; bi-functionality; spinal cord; optic nerve; peripheral nerve; Schwann cells; regeneration
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Dun, X.-P.; Parkinson, D.B. Role of Netrin-1 Signaling in Nerve Regeneration. Int. J. Mol. Sci. 2017, 18, 491.

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