Epidermal growth factor receptor antagonists and CNS axon regeneration: mechanisms and controversies.

Abstract

The reasons for the failure of central nervous system (CNS) axons to regenerate include the presence of myelin- and non-myelin derived inhibitory molecules, neuronal apoptosis and the absence of a potent neurotrophic stimulus. Transactivation of the epidermal growth factor receptor (EGFR) has been implicated in signalling inhibition of axon growth in the CNS. Small molecule EGFR inhibitors such as AG1478 and PD168393 promote CNS axon growth after optic nerve transection despite the presence of inhibitory molecules in the environment of the regenerating axon. However, our results demonstrate that phosphorylated EGFR (pEGFR) is not present on regenerating axons and that the majority of pEGFR is present in glia, suggesting that EGFR cannot play a direct intra-axonal role in signalling inhibition and thus disinhibited CNS axon growth must be indirectly mediated by glia. We argue that EGFR may not have a role in signalling axon growth inhibition since AG1478 and PD168393 promotes neuronal neurite outgrowth in CNS myelin-inhibited cultures after EGFR knockdown. This review discusses the current evidences for and against the involvement of EGFR in signalling myelin inhibition.

• Authors: Martin Berry, Zubair Ahmed, Michael R Douglas, Ann Logan
• Journal: Brain research bulletin (Brain Res Bull) Vol. 84 Issue 4-5 Pg. 289-99 (Mar 10 2011) ISSN: 1873-2747 [Electronic] United States
• PMID: 20709162 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• ErbB Receptors

Topics

• Animals
• Axons (pathology, physiology)
• Brain Injuries (drug therapy, pathology)
• Central Nervous System (anatomy & histology, pathology, physiology)
• Drug Discovery
• ErbB Receptors (antagonists & inhibitors)
• Humans
• Myelin Sheath (metabolism)
• Nerve Regeneration (physiology)
• Neuroglia (metabolism)
• Signal Transduction (physiology)
• Spinal Cord Injuries (drug therapy, pathology)