What Is the Role of the Rho-ROCK Pathway in Neurologic Disorders?

Rho-associated coiled-coil containing kinases (ROCK), including ROCK1 and ROCK2, are the primary effectors of the Rho family of small guanosine triphosphatases (GTPases)1 (Figure). The Rho/ROCK signaling pathway has a critical role in regulating the cytoskeleton dynamics responsible for cell adhesion, proliferation, motility, and contraction.2,3 In the nervous system, ROCK proteins phosphorylate a wide variety of transduction molecules that regulate axonal growth during development and after injury; dendritic growth and spine remodeling underlying synaptic plasticity; cell survival through cross talk with other signal transduction pathways; and glial activation and function, including neuroinflammation.4-7 Experimental studies using ROCK antagonists or RNA interference approaches indicate that Rho/ROCK signaling may have a major role in the pathogenesis of a wide range of neurologic and non-neurologic disorders. Not surprisingly, ROCK inhibition has been extensively explored as an emerging therapeutic target in several disease models. There are several comprehensive reviews on these topics.2,3,8-14 Some of the basic concepts on Rho/ROCK signaling, its effects in the nervous system, and its potential implications in the pathogenesis and as a therapeutic target in neurologic disorders, will be briefly emphasized in this study.