NDLI: Anti-Ganglioside Antibody-Mediated Activation of RhoA Induces Inhibition of Neurite Outgrowth

Content Provider	PubMed Central
Author	Zhang, Gang Lehmann, Helmar C. Manoharan, Sowmia Hashmi, Md. Ali Shim, Sangwoo Ming, Guo-li Schnaar, Ronald L. Lopez, Pablo H. Bogdanova, Nataliia Sheikh, Kazim A.
Copyright Year	2011
Abstract	Anti-ganglioside antibodies (Abs) are strongly associated with axonal forms of Guillain Barré syndrome (GBS). Some studies indicate that these Abs, including those with GD1a reactivity, are associated with poor prognosis and/or incomplete recovery. We recently demonstrated that a disease-relevant anti-ganglioside Ab with GD1a reactivity inhibits axon regeneration after PNS injury in an animal model (Lehmann et al., 2007). An implication of these findings is that anti-GD1a Abs can mediate inhibition of axon regeneration and limit recovery in some patients with GBS. The downstream inhibitory intracellular signaling that mediates anti-ganglioside Ab-induced axon inhibition remains unclear. In the current study, we show that disease-relevant and GBS patient's anti-ganglioside Abs can inhibit neurite outgrowth in dissociated primary neuronal cultures. Activation of small GTPase RhoA and its key downstream effector Rho kinase (ROCK) are critical mediators of growth cone and neurite outgrowth inhibition. Therefore, we examined the role of these intracellular signaling molecules in our primary neuronal cultures by molecular and pharmacologic approaches. Our results show that the Ab-mediated inhibition of neurite outgrowth involves the activation of RhoA and ROCK pathway and this activation is through the engagement of specific cell-surface gangliosides by Abs. In summary, these studies directly link patient autoantibodies to an intracellular inhibitory signaling pathway involved in anti-ganglioside Ab-mediated inhibition of neurite outgrowth.
Related Links	http://dx.doi.org/10.1523/jneurosci.3829-10.2011
Ending Page	1675
Page Count	12
Starting Page	1664
File Format	PDF
ISSN	02706474
e-ISSN	15292401
Journal	The Journal of Neuroscience
Issue Number	5
Volume Number	31
Language	English
Publisher	Society for Neuroscience
Publisher Date	2011-02-02
Access Restriction	Open
Rights Holder	Society for Neuroscience
Subject Keyword	Neuroscience(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience

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