title: Cerebral cavernous malformation is a vascular disease associated with activated RhoA signaling.
abstract: Cerebral cavernous malformation (CCM) involves the homozygous inactivating mutations of one of three genes, ccm1, -2, or -3 resulting in hyperpermeable blood vessels in the brain. The CCM1, -2, and -3 proteins form a complex to organize the signaling networks controlling endothelial cell physiology including actin dynamics, tube formation, and adherens junctions. The common biochemical defect with the loss of CCM1, -2, or -3 is increased RhoA activity leading to the activation of Rho-associated coiled coil-forming kinase (ROCK). Inhibition of the ROCK rescues CCM endothelial cell dysfunction, suggesting that the inhibition of RhoA-ROCK signaling may be a therapeutic strategy to prevent or arrest the progression of the CCM lesions.
authors.affiliation: Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Richardson
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Dibble
authors.forename: Asya L
authors.initials: AL
authors.lastname: Borikova
authors.forename: Gary L
authors.initials: GL
authors.lastname: Johnson
mesh_terms: D000818:Animals; D020786:Hemangioma, Cavernous, Central Nervous System / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D014652:Vascular Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein