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The pathogenetic features of cerebral cavernous malformations: a comprehensive review with therapeutic implications Krisht KM; Whitehead KJ; Niazi T; Couldwell WTNeurosurg Focus 2010[Sep]; 29 (3): E2Cerebral cavernous malformations (CCMs) are common vascular lesions of the CNS that may lead to seizures, focal neurological deficits, and fatal hemorrhagic stroke. Human genetic studies have identified 3 genes associated with CCM, and biochemical and molecular studies in mice have elucidated signaling pathways with important therapeutic implications. In this review, the authors shed light on the 3 discovered CCM genes as well as their protein products, with particular emphasis on their signal transduction pathways and their interaction with one another. Close focus is directed at mice model studies involving the Ccm2 gene product signaling pathway, revealing an important role for the use of simvastatin or other RhoA inhibitors as a therapeutic modality in the treatment of CCM. The remaining challenges to creating a more faithful CCM animal model as well as future clinical and research implications are reviewed.|Animals[MESH]|Apoptosis Regulatory Proteins/genetics/physiology[MESH]|Carrier Proteins/genetics/physiology[MESH]|Disease Models, Animal[MESH]|Hemangioma, Cavernous, Central Nervous System/drug therapy/*genetics/pathology[MESH]|Humans[MESH]|KRIT1 Protein[MESH]|Membrane Proteins/genetics/physiology[MESH]|Mice[MESH]|Microtubule-Associated Proteins/genetics/physiology[MESH]|Proto-Oncogene Proteins/genetics/physiology[MESH]|Signal Transduction/*genetics/physiology[MESH]|Simvastatin/therapeutic use[MESH] |
