FUNCTIONAL ANALYSIS OF THE TANGIER DISEASE GENE ABC1

在西方社会，心血管疾病是导致死亡的主要原因。升高的循环高密度脂蛋白（HDL）水平被认为通过介导胆固醇转运出外周组织来防止疾病状态。然而，这一过程背后的分子机制尚未完全表征。最近发现的丹吉尔病基因产物（ABC1），当在人类中发生突变时，会导致循环HDL下降到无法检测的水平，这为逆向胆固醇运输过程提供了额外的分子见解。这一应用提出了ABC1在细胞定位方面的结构-功能分析，ABC1的蛋白质-蛋白质分子描述与HDL动员细胞内胆固醇酯储存的能力有关，将有助于开发心血管疾病的新疗法。

Cardiovascular disease is the leading cause of mortality in western societies. Increased levels of circulating high-density lipoproteins (HDL) are thought to protect against the disease state by mediating cholesterol transport out of peripheral tissues. However, the molecular mechanisms underlying this process are incompletely characterized. The recent identification of the Tangier disease gene product (ABC1), which when mutated in human causes circulating HDL to drop to undetectable levels, has provided additional molecular insight into the process of reverse cholesterol transport. This application proposes to a structure-function analysis of ABC1 in terms of its cellular localization, protein-protein molecular description of ABC1 in relation to the ability of HDL to mobilize intracellular stores of cholesterol-esters will be helpful in the development of novel therapies for cardiovascular disease.