Cerebral cavernous malformations as a disease of vascular permeability: from bench to bedside with caution.
Tremendous insight into the molecular and genetic pathogenesis of cerebral cavernous malformations (CCMs) has been gained over the past 2 decades. This includes the identification of 3 distinct genes involved in familial CCMs. Still, a number of unanswered questions regarding the process from gene mutation to vascular malformation remain. It is becoming more evident that the disruption of interendothelial junctions and ensuing vascular hyperpermeability play a principal role. The purpose of this review is to summarize the current understanding of CCM genes, associated proteins, and functional pathways. Promising molecular and genetic therapies targeted at identified molecular aberrations are discussed as well.
Yadla
Sanjay
S
Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Jabbour
Pascal M
PM
Shenkar
Robert
R
Shi
Changbin
C
Campbell
Peter G
PG
Awad
Issam A
IA
D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002199:Capillary Permeability / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics; D004730:Endothelium, Vascular / Q000503:physiopathology; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007365:Intercellular Junctions / Q000235:genetics / Q000502:physiology; D002538:Intracranial Arteriovenous Malformations / Q000378:metabolism / Q000503:physiopathology; D000075927:KRIT1 Protein; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C502544:CCM2 protein, human; D002352:Carrier Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins
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