Implication of Rho GTPases in Neurodegenerative Diseases

Judith      Antoine-Bertrand; Josee-France      Villemure; Nathalie      Lamarche-Vane

Abstract

The establishment of neural connectivity implicates tight regulation of the intracellular signaling pathways mediated by axon guidance molecules. The Rho family of small GTPases, in particular Rho, Rac, and Cdc42, are important regulators of the cytoskeleton in neuronal cells acting, downstream of most, if not all, guidance cue receptors. Furthermore, recent studies using in vivo knockout mouse models provide new evidence of the primary role played by Rho GTPase signaling during the development of the nervous system. Here, we review our recent understanding of Rho GTPase signaling in response to classical axon guidance cues in mammalian cells. We also describe how in vivo knockout mouse models have been useful to implicate Rho GTPase signaling during the formation of the nervous system. Finally, we present several lines of evidence showing the involvement of Rho GTPase signaling in the development and progression of neurodegenerative diseases.

Keywords: Rho GTPases, axon guidance, knockout mouse models, neurodegenerative diseases, ephrins, semaphorins, netrin, synaptic plasticity, neuronal migration