Enhanced Neurite Outgrowth of Human Model (NT2) Neurons by Small-Molecule Inhibitors of Rho/ROCK Signaling

摘要: Axonal injury in the adult human central nervous system often results loss of sensation and motor functions. Promoting regeneration severed axons requires inactivation growth inhibitory influences from tissue environment stimulation neuron intrinsic potential. Especially glial cell derived factors, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, myelin general, prevent axon regeneration. Most inhibiting factors converge onto Rho/ROCK signaling pathway neurons. Although conditions injured are clearly different those during neurite outgrowth vitro, here we use a chemical approach to manipulate signalling with small-molecule agents encourage culture. The development therapeutic treatments drug testing not only on neurons experimental animals, but also Using NT2 model neurons, demonstrate that pain reliever Ibuprofen decreases RhoA (Ras homolog gene family, member A GTPase) activation promotes growth. Inhibition downstream effector Rho kinase by Y-27632 strong increase outgrowth. Conversely, lysophosphatidic acid cone collapse eventually retraction. Finally, show blocking kinase, an bearing neurites. Due its anti-inflammatory promoting action, pharmacological treatment damaged neural should be explored.