CCM3 and cerebral cavernous malformation disease

Abstract

Cerebral cavernous malformations (CCMs) are vascular lesions characterised by enlarged and irregular structure of small blood vessels in the brain, which can result in increased risk of stroke, focal neurological defects and seizures. Three different genes, CCM1/Krev/Rap1 Interacting Trapped 1, CCM2/MGC4607 and CCM3/PDCD10, are associated with the CCMs’ progression, and mutations in one of three CCM genes cause CCM disease. These three CCM proteins have similar function in maintaining the normal structure of small blood vessels. However, CCM3 mutation results in a more severe form of the disease which may suggest that CCM3 has unique biological function in the vasculature. The current review focuses on the signalling pathways mediated by CCM3 in regulating endothelial cell junction, proliferation, migration and permeability. These findings may offer potential therapeutic strategies for the treatment of CCMs.