Anti-glycan antibodies halt axon regeneration in a model of guillain Barrè syndrome axonal neuropathy by inducing microtubule disorganization via RhoA-ROCK-dependent inactivation of CRMP-2.

Anti-glycan antibodies halt axon regeneration in a model of guillain Barrè syndrome axonal neuropathy by inducing microtubule disorganization via RhoA-ROCK-dependent inactivation of CRMP-2.
Exp Neurol. 2016 Jan 21;
Authors: Salvador VR, Heredia F, Berardo A, Palandri A, Wojnacki J, Vivinetto AL, Sheikh KA, Caceres A, Lopez PH
Abstract
Several reports have linked the presence of high titers of anti-Gg Abs with delayed recovery/poor prognosis in GBS. In most cases, failure to recover is associated with halted/deficient axon regeneration. Previous work identified that monoclonal and patient-derived anti-Gg Abs can act as inhibitory factors in an animal model of axon regeneration. Further studies using primary dorsal root ganglion neuron (DRGn) cultures demonstrated that anti-Gg Abs can inhibit neurite outgrowth by targeting gangliosides via activation of the small GTPase RhoA and its associated kinase (ROCK), a signaling pathway common to other established inhibitors of axon regeneration. We aimed to study the molecular basis of the inhibitory effect of anti-Gg abs on neurite outgrowth by dissecting the molecular dynamics of growth cones (GC) cytoskeleton in relation to the spatial-temporal analysis of RhoA activity. We now report that axon growth inhibition in DRGn induced by a well characterized mAb targeting gangliosides GD1a/GT1b involves: i) an early RhoA/ROCK-independent collapse of lamellipodia; ii) a RhoA/ROCK-dependent shrinki...

Source: Experimental Neurology - January 21, 2016 Category: Neurology Authors: Salvador VR, Heredia F, Berardo A, Palandri A, Wojnacki J, Vivinetto AL, Sheikh KA, Caceres A, Lopez PH Tags: Exp Neurol Source Type: research