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
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
SN - 1460-2156
VL - 129
SP - 490
EP - 502
JO - Brain
JF - Brain
ER -