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Int. J. Mol. Sci. 2017, 18(3), 491;

Role of Netrin-1 Signaling in Nerve Regeneration

Peninsula Schools of Medicine and Dentistry, Plymouth University, Plymouth, Devon PL6 8BU, UK
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)
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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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