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

Research output: Contribution to journalArticle

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)490-502
Number of pages13
JournalBrain
Volume129
Publication statusPublished - 26 Oct 2005

Keywords

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