Autoantobodies activate small GTPase RhoA to modulate neurite outgrowth

This review illustrates an example of adaptive immune responses (auto-antibodies) modulating growth/repair behavior of neurons in the disease context of Guillain-Barré syndrome (GBS), which is a prototypic autoimmune, acute monophasic disorder of the peripheral nerves that is the commonest cause of acute flaccid paralysis worldwide. Anti-ganglioside antibodies (Abs) are the most commonly recognized autoimmune markers in all forms of GBS and these Abs are associated with poor recovery. Extent of axonal injury and failure of axonal regeneration are critical determinants of recovery after GBS. In this clinical context, our group examined the hypothesis that anti-ganglioside Abs adversely affect axon regeneration after peripheral nerve injury. We show that anti-ganglioside Abs inhibit axon regeneration in preclinical cell culture and animal models. This inhibition is mediated by activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) by modulation of growth cone extension and associated neurite elongation in neuronal cultures. Our studies suggest that RhoA and ROCK are potential targets for development of novel therapeutic strategies to enhance nerve repair.