For at least two decades, members of the Rho family of GTPases (Rho, Rac, and Cdc42) have been recognized as central regulators of neuronal morphology and crucial players in the proper development and function of the nervous system. Based largely on their capacity to influence actin cytoskeletal dynamics, these GTPases act as master regulators of processes critical to synaptic growth and remodeling, including axonal extension, neurite outgrowth, and dendritic spine morphogenesis. In most cases, Rac promotes these effects while Rho opposes them. This antagonistic relationship dictates that the balance between Rac- and Rho-dependent signaling pathways is a key determinant of neuronal morphology.
Further studies have revealed expanding roles for Rho family GTPases in other critical cellular processes. Most recently, Rho family GTPases have been discovered to play significant roles in neuronal survival and death. Intriguingly, much like their antagonistic roles in the regulation of neuronal morphology, Rac and Rho appear to have opposing effects on neuronal survival as well. Typically, Rac and its downstream effectors promote neuronal survival, while Rho and its downstream effectors are capable of inducing neuronal apoptosis. Thus, maintaining a balance between these Rac-dependent pro-survival signals and Rho-dependent pro-apoptotic signals is essential to the survival of many types of neurons.
In this Research Topic, we welcome reviews and original research papers focused on elucidating the role of Rho family GTPases and their downstream effectors in regulating neuronal survival and death. In particular, we are interested in highlighting Rho family GTPase-dependent pathways that underlie the pathogenic mechanisms of neurodegenerative disorders like Alzheimer's disease and amyotrophic lateral sclerosis. A thorough investigation of these topics may reveal novel sites for therapeutic intervention which target Rho family GTPase signaling pathways.
For at least two decades, members of the Rho family of GTPases (Rho, Rac, and Cdc42) have been recognized as central regulators of neuronal morphology and crucial players in the proper development and function of the nervous system. Based largely on their capacity to influence actin cytoskeletal dynamics, these GTPases act as master regulators of processes critical to synaptic growth and remodeling, including axonal extension, neurite outgrowth, and dendritic spine morphogenesis. In most cases, Rac promotes these effects while Rho opposes them. This antagonistic relationship dictates that the balance between Rac- and Rho-dependent signaling pathways is a key determinant of neuronal morphology.
Further studies have revealed expanding roles for Rho family GTPases in other critical cellular processes. Most recently, Rho family GTPases have been discovered to play significant roles in neuronal survival and death. Intriguingly, much like their antagonistic roles in the regulation of neuronal morphology, Rac and Rho appear to have opposing effects on neuronal survival as well. Typically, Rac and its downstream effectors promote neuronal survival, while Rho and its downstream effectors are capable of inducing neuronal apoptosis. Thus, maintaining a balance between these Rac-dependent pro-survival signals and Rho-dependent pro-apoptotic signals is essential to the survival of many types of neurons.
In this Research Topic, we welcome reviews and original research papers focused on elucidating the role of Rho family GTPases and their downstream effectors in regulating neuronal survival and death. In particular, we are interested in highlighting Rho family GTPase-dependent pathways that underlie the pathogenic mechanisms of neurodegenerative disorders like Alzheimer's disease and amyotrophic lateral sclerosis. A thorough investigation of these topics may reveal novel sites for therapeutic intervention which target Rho family GTPase signaling pathways.