RT Journal Article
SR Electronic
T1 Inactivation of Rho Signaling Pathway Promotes CNS Axon Regeneration
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7537
OP 7547
DO 10.1523/JNEUROSCI.19-17-07537.1999
VO 19
IS 17
A1 Maxine Lehmann
A1 Alyson Fournier
A1 Immaculada Selles-Navarro
A1 Pauline Dergham
A1 Agnes Sebok
A1 Nicole Leclerc
A1 Gabor Tigyi
A1 Lisa McKerracher
YR 1999
UL http://www.jneurosci.org/content/19/17/7537.abstract
AB Regeneration in the CNS is blocked by many different growth inhibitory proteins. To foster regeneration, we have investigated a strategy to block the neuronal response to growth inhibitory signals. Here, we report that injured axons regrow directly on complex inhibitory substrates when Rho GTPase is inactivated. Treatment of PC12 cells with C3 enzyme to inactivate Rho and transfection with dominant negative Rho allowed neurite growth on inhibitory substrates. Primary retinal neurons treated with C3 extended neurites on myelin-associated glycoprotein and myelin substrates. To explore regeneration in vivo, we crushed optic nerves of adult rat. After C3 treatment, numerous cut axons traversed the lesion to regrow in the distal white matter of the optic nerve. These results indicate that targeting signaling mechanisms converging to Rho stimulates axon regeneration on inhibitory CNS substrates.