Work

Cerebral cavernous malformation is a vascular disease associated with activated RhoA signaling

Year: 2012

Type: article

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.

Source: Biological Chemistry

DOI: 10.1515/hsz-2012-0243

Authors: Bryan T. Richardson, Christopher F. Dibble, Asya L. Borikova, Gary L. Johnson

Institutions: University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center

Language: English

Topic: Vascular Malformations Diagnosis and Treatment

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences