Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases

Small guanosine triphosphatases (GTPases) of the Ras superfamily are key regulators of many key cellular events such as proliferation, differentiation, cell cycle regulation, migration, or apoptosis. To control these biological responses, GTPases activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and in some small GTPases also guanine nucleotide dissociation inhibitors (GDIs). Moreover, small GTPases transduce signals by their downstream effector molecules. Many studies demonstrate that small GTPases of the Ras family are involved in neurodegeneration processes. Here, in this review, we focus on the signaling pathways controlled by these small protein superfamilies that culminate in neurodegenerative pathologies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Specifically, we concentrate on the two most studied families of the Ras superfamily: the Ras and Rho families. We summarize the latest findings of small GTPases of the Ras and Rho families in neurodegeneration in order to highlight these small proteins as potential therapeutic targets capable of slowing down different neurodegenerative diseases.A.A.S. is a recipient of a predoctoral fellowship (PRE_2017_1_0016) from the Basque Government. M.L.M. is a recipient of a fellowship from Foundation “Jesús de Gangoiti y Barrera”. J.L.Z. was supported by the Instituto de Salud Carlos III (PI18/00207) and the University of Basque Country Grant (US19/04)http://creativecommons.org/licenses/by/3.0/es