Inhibiting Smad signaling promotes neuron regeneration

Abstract

Regeneration of a lesioned CNS axon of a mature neuron, determined to be subject to regeneration inhibition by Smad2/3 signaling, is promoted by contacting the neuron with an inhibitor of Smad2/3 signaling sufficient to promote regeneration of the axon.

1 . A method of promoting neurite outgrowth, the method comprising the steps of:
 (a) contacting the neuron in situ with an inhibitor of Smad2/3 signaling; and   (b) detecting a resultant promotion of neurite outgrowth of the neuron, wherein the neuron is an adult dorsal root ganglion (DRG) cell, and the inhibitor is selected from the group consisting of 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide (SB-431542), -2-(5-benzo[1,3]dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride (SB-505124) and 4-{4-[3-(Pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H-pyran-4-yl)benzamide (GW788388).   
   
   
       2 - 13 . (canceled) 
   
   
       14 . The method of  claim 1  wherein the inhibitor is 2-(5-benzo[1,3]dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride (SB-505124). 
   
   
       15 . A method of promoting neurite outgrowth, the method comprising the steps of:
 (a) contacting the neuron in situ with an inhibitor of Smad2/3 signaling;   (b) isolating and culturing the neuron in vitro; and   (c) detecting a resultant promotion of neurite outgrowth of the neuron in vitro, wherein the neuron is an adult dorsal root ganglion (DRG) cell and the inhibitor is selected from the group consisting of 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide (SB-431542), 2-(5-benzo[1,3]dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6-methylpyridine hydrochloride (SB-505124) and 4-{4-[3-(Pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H-pyran-4-yl)benzamide (GW788388).