Department of Neurosurgery, University of Utah, Salt Lake City, Utah 84132, USA.
Neurosurg Focus. 2010 Sep;29(3):E2. doi: 10.3171/2010.6.FOCUS10135.
Cerebral 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.
脑静脉畸形（CCM）是中枢神经系统常见的血管病变，可能导致癫痫发作、局灶性神经功能缺损和致命性出血性卒中。人类遗传学研究已经确定了与 CCM 相关的 3 个基因，而小鼠的生化和分子研究则阐明了具有重要治疗意义的信号通路。在这篇综述中，作者阐述了已发现的 3 个 CCM 基因及其蛋白产物，特别强调了它们的信号转导通路及其相互作用。研究重点集中在涉及 Ccm2 基因产物信号通路的小鼠模型研究上，揭示了使用辛伐他汀或其他 RhoA 抑制剂作为 CCM 治疗方法的重要作用。还回顾了创建更真实的 CCM 动物模型以及未来临床和研究意义所面临的挑战。
