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。循环中高密度脂蛋白(高密度脂蛋白)水平的增加被认为通过调节胆固醇从周围组织中转移来预防疾病状态。然而，这一过程背后的分子机制尚不完全清楚。最近丹吉尔病基因产物(ABC1)的发现，当它在人类中突变时，会导致循环中的高密度脂蛋白下降到无法检测的水平，这为胆固醇反向运输过程提供了更多的分子洞察力。从细胞定位的角度对ABC1的结构和功能进行分析，从蛋白质和蛋白质分子的角度描述ABC1与高密度脂蛋白动员细胞内胆固醇酯储存的能力，将有助于心血管疾病新疗法的开发。

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.