Molecular pathways for intracellular cholesterol accumulation: Common pathogenic mechanisms in Niemann-Pick disease Type C and cystic fibrosis
Molecular pathways for intracellular cholesterol accumulation: Common pathogenic mechanisms in Niemann-Pick disease Type C and cystic fibrosis
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DOI：
10.1016/j.abb.2011.08.012
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发表时间：
2011-11-01
影响因子：
3.9
通讯作者：
Kelley, Thomas J.
中科院分区：
文献类型：
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作者：
Cianciola, Nicholas L.;Carlin, Cathleen R.;Kelley, Thomas J.
自从首次发现C型尼曼-皮克病的潜在遗传缺陷以来，还不到20年。这些缺陷损害了两种直接参与脂类运输的蛋白质的功能，导致游离胆固醇沉积在晚期的内体隔室，并对细胞功能和临床表现产生了多种影响。这一领域的快速研究极大地提高了我们对细胞内胆固醇动态平衡的整体理解。过多的胆固醇积聚也与一些与遗传无关的疾病的临床表现有关，包括囊性纤维化。在囊性纤维化中应用异常细胞信号行为的知识，为在Niemann-Pick病C型中识别类似以前未知的疾病途径开辟了前景。认识到Niemann-Pick病C型和囊性纤维化都会损害胆固醇调节途径，这也为确定共同的治疗靶点提供了理论基础。(C)2011 Elsevier Inc.保留所有权利。
It has been less than two decades since the underlying genetic defects in Niemann-Pick disease Type C were first identified. These defects impair function of two proteins with a direct role in lipid trafficking, resulting in deposition of free cholesterol within late endosomal compartments and a multitude of effects on cell function and clinical manifestations. The rapid pace of research in this area has vastly improved our overall understanding of intracellular cholesterol homeostasis. Excessive cholesterol buildup has also been implicated in clinical manifestations associated with a number of genetically unrelated diseases including cystic fibrosis. Applying knowledge about anomalous cell signaling behavior in cystic fibrosis opens prospects for identifying similar previously unrecognized disease pathways in Niemann-Pick disease Type C. Recognition that Niemann-Pick disease Type C and cystic fibrosis both impair cholesterol regulatory pathways also provides a rationale for identifying common therapeutic targets. (C) 2011 Elsevier Inc. All rights reserved.