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

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Epidermal growth factor receptor antagonists and CNS axon regeneration: Mechanisms and controversies. / Berry, Martin; Ahmed, Zubair; Douglas, Michael; Logan, Ann.

In: Brain Research Bulletin, Vol. 84, 13.08.2010, p. 289-299.

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@article{c57135ad479147019a45b4c6ad2f54d5,
title = "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.",
author = "Martin Berry and Zubair Ahmed and Michael Douglas and Ann Logan",
year = "2010",
month = aug
day = "13",
doi = "10.1016/j.brainresbull.2010.08.004",
language = "English",
volume = "84",
pages = "289--299",
journal = "Brain Research Bulletin",
issn = "0361-9230",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Epidermal growth factor receptor antagonists and CNS axon regeneration: Mechanisms and controversies.

AU - Berry, Martin

AU - Ahmed, Zubair

AU - Douglas, Michael

AU - Logan, Ann

PY - 2010/8/13

Y1 - 2010/8/13

N2 - 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.

AB - 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.

U2 - 10.1016/j.brainresbull.2010.08.004

DO - 10.1016/j.brainresbull.2010.08.004

M3 - Review article

C2 - 20709162

VL - 84

SP - 289

EP - 299

JO - Brain Research Bulletin

JF - Brain Research Bulletin

SN - 0361-9230

ER -