Cerebral cavernous malformations: from genes to proteins to disease Clinical article
Cerebral cavernous malformations: from genes to proteins to disease Clinical article
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DOI：
10.3171/2011.8.jns101241
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发表时间：
2012-01-01
影响因子：
4.1
通讯作者：
Preul, Mark C.
中科院分区：
文献类型：
--
作者：
Cavalcanti, Daniel D.;Kalani, M. Yashar S.;Preul, Mark C.
在过去的半个世纪中，分子生物学在我们对血管和血管发生的理解以及对这些过程出错导致的畸形的治疗方面取得了巨大进展。鉴于其散发性和家族性分布，其发育和病理学联系毛细血管扩张症，以及其观察到的染色体异常，脑海绵状血管畸形（CCM）被认为是类似于癌性生长。虽然CCM形成的确切病理机制还不清楚，但3个遗传位点的鉴定已开始阐明CCM发病机制中涉及的关键发育途径。海绵状血管畸形可以是偶发性的，也可以是常染色体显性的。CCM的家族性形式归因于涉及调节重要过程（如血管生成前体和凋亡机制成员的增殖和分化）的3个不同基因座的突变。这些过程对于体内每一个血管的生成、维护和修剪都很重要。在这篇综述中，作者强调了有关CCM分子遗传学的最新发现，突出了治疗这些病变的潜在新治疗靶点。(DOI：10.3171/2011.8.JNS101241）
Over the past half century molecular biology has led to great advances in our understanding of angio- and vasculogenesis and in the treatment of malformations resulting from these processes gone awry. Given their sporadic and familial distribution, their developmental and pathological link to capillary telangiectasias, and their observed chromosomal abnormalities, cerebral cavernous malformations (CCMs) are regarded as akin to cancerous growths. Although the exact pathological mechanisms involved in the formation of CCMs are still not well understood, the identification of 3 genetic loci has begun to shed light on key developmental pathways involved in CCM pathogenesis. Cavernous malformations can occur sporadically or in an autosomal dominant fashion. Familial forms of CCMs have been attributed to mutations at 3 different loci implicated in regulating important processes such as proliferation and differentiation of angiogenic precursors and members of the apoptotic machinery. These processes are important for the generation, maintenance, and pruning of every vessel in the body. In this review the authors highlight the latest discoveries pertaining to the molecular genetics of CCMs, highlighting potential new therapeutic targets for the treatment of these lesions. (DOI: 10.3171/2011.8.JNS101241)