Neurotrophic factor synergy is required for neuronal survival and disinhibited axon regeneration after CNS injury

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@article{8d0b9f1f9b83450cbf201087d87ac58a,
title = "Neurotrophic factor synergy is required for neuronal survival and disinhibited axon regeneration after CNS injury",
abstract = "The therapeutic effects of individual neurotrophic factors (NTF) have proved disappointing in clinical trials for neuronal repair and axon regeneration. Here, we demonstrate NTF synergistic neuronal responses after a combination of basic fibroblast growth factor, neurotrophin-3 and brain derived growth factor delivered to the somata of retinal ganglion cells promoted greater survival and axon growth than did the sum of the effects of each NTF alone. Triple and not single NTF treatments potentiated regulated intramembraneous proteolysis of p75(NTR), and ectodomain shedding of Nogo receptor, correlated with a 30% decrease in activation of Rho-A, a key signalling molecule in the axon growth inhibitory cascade. Thus, combinatorial NTF administration synergistically enhanced neuronal survival, disinhibited axon growth and promoted axon regeneration through the hostile CNS environment without the intervention of scar tissue at the lesion site.",
keywords = "optic nerve regeneration, CNS, p75(NTR), neurotrophic factors, regulated intramembrane proteolysis",
author = "Ann Logan and Zubair Ahmed and Andrew Baird and Ana Gonzalez and Martin Berry",
year = "2005",
month = oct
day = "26",
doi = "10.1093/brain/awh706",
language = "English",
volume = "129",
pages = "490--502",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - Neurotrophic factor synergy is required for neuronal survival and disinhibited axon regeneration after CNS injury

AU - Logan, Ann

AU - Ahmed, Zubair

AU - Baird, Andrew

AU - Gonzalez, Ana

AU - Berry, Martin

PY - 2005/10/26

Y1 - 2005/10/26

N2 - The therapeutic effects of individual neurotrophic factors (NTF) have proved disappointing in clinical trials for neuronal repair and axon regeneration. Here, we demonstrate NTF synergistic neuronal responses after a combination of basic fibroblast growth factor, neurotrophin-3 and brain derived growth factor delivered to the somata of retinal ganglion cells promoted greater survival and axon growth than did the sum of the effects of each NTF alone. Triple and not single NTF treatments potentiated regulated intramembraneous proteolysis of p75(NTR), and ectodomain shedding of Nogo receptor, correlated with a 30% decrease in activation of Rho-A, a key signalling molecule in the axon growth inhibitory cascade. Thus, combinatorial NTF administration synergistically enhanced neuronal survival, disinhibited axon growth and promoted axon regeneration through the hostile CNS environment without the intervention of scar tissue at the lesion site.

AB - The therapeutic effects of individual neurotrophic factors (NTF) have proved disappointing in clinical trials for neuronal repair and axon regeneration. Here, we demonstrate NTF synergistic neuronal responses after a combination of basic fibroblast growth factor, neurotrophin-3 and brain derived growth factor delivered to the somata of retinal ganglion cells promoted greater survival and axon growth than did the sum of the effects of each NTF alone. Triple and not single NTF treatments potentiated regulated intramembraneous proteolysis of p75(NTR), and ectodomain shedding of Nogo receptor, correlated with a 30% decrease in activation of Rho-A, a key signalling molecule in the axon growth inhibitory cascade. Thus, combinatorial NTF administration synergistically enhanced neuronal survival, disinhibited axon growth and promoted axon regeneration through the hostile CNS environment without the intervention of scar tissue at the lesion site.

KW - optic nerve regeneration

KW - CNS

KW - p75(NTR)

KW - neurotrophic factors

KW - regulated intramembrane proteolysis

UR - http://www.scopus.com/inward/record.url?scp=31544478557&partnerID=8YFLogxK

U2 - 10.1093/brain/awh706

DO - 10.1093/brain/awh706

M3 - Article

C2 - 16339795

VL - 129

SP - 490

EP - 502

JO - Brain

JF - Brain

SN - 0006-8950

ER -