abstract |
This invention provides for the use of antagonists of Rho, or proteins related to Rho as therapeutic targets for agents designed to block growth inhibition by myelin or myelin proteins. One embodiment pertains to the use of Rho antagonists that foster axon regeneration in the central nervous system. The therapeutic agent or antagonist can be small molecules, proteins or peptides, or any agent that binds to Rho or its family members to inactivate this patheway. Embodiments include: the use of the Rho regulatory pathway as a target for Rho antagonists; the use of GDP dissociation inhibitors (GDIs) inhibit the dissociation of GDP from Rho, and thereby prevent the binding of GTP necessary for the activation of Rho; the use of Rho specific GTPase activating protein (GAPs) as targets for the regulation of Rho activity; the use of agents that promote Rho binding to GDI, and block Rho binding to the plasma membrane are also considered within the scope of this invention; the use of C3 transferase and related toxins such as A and B, with related Rho-inhibitory activity to inactivate Rho and stimulate axon growth; the use of dominant negative forms of Rho, used to inactivate Rho, to foster axon growth. |