Dock GEFs and their therapeutic potential: neuroprotection and axon regeneration.

Abstract

The dedicator of cytokinesis (Dock) family is composed of atypical guanine exchange factors (GEFs) that activate the Rho GTPases Rac1 and Cdc42. Rho GTPases are best documented for their roles in actin polymerization and they regulate important cellular functions, including morphogenesis, migration, neuronal development, and cell division and adhesion. To date, 11 Dock family members have been identified and their roles have been reported in diverse contexts. There has been increasing interest in elucidating the roles of Dock proteins in recent years and studies have revealed that they are potential therapeutic targets for various diseases, including glaucoma, Alzheimer's disease, cancer, attention deficit hyperactivity disorder and combined immunodeficiency. Among the Dock proteins, Dock3 is predominantly expressed in the central nervous system and recent studies have revealed that Dock3 plays a role in protecting retinal ganglion cells from neurotoxicity and oxidative stress as well as in promoting optic nerve regeneration. In this review, we discuss the current understanding of the 11 Dock GEFs and their therapeutic potential, with a particular focus on Dock3 as a novel target for the treatment of glaucoma and other neurodegenerative diseases.