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

被引：125

作者：

Logan, A ^{[1
]}

Ahmed, Z ^{[1
]}

Baird, A ^{[1
]}

Gonzalez, AM ^{[1
]}

Berry, M ^{[1
]}

机构：

[1] Univ Birmingham, Mol Neurosci Grp, Div Med Sci, Birmingham B15 2TT, W Midlands, England

来源：

BRAIN | 2006年 / 129卷

基金：

英国惠康基金;

关键词：

neurotrophic factors; regulated intramembrane proteolysis; optic nerve regeneration; p75(NTR); CNS;

D O I：

10.1093/brain/awh706

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：490 / 502

页数：13

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