THE NIEMANN-PICK DISEASE GENES REGULATORS OF CELLULAR CHOLESTEROL HOMEOSTASIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。细胞胆固醇稳态是通过激活指定的固醇调节元件结合蛋白和肝脏X受体转录途径来维持的。通过对尼曼-皮克C （NPC）病的研究，对调节这些途径的分子机制有了深入的了解。NPC1和NPC2疾病基因的突变导致胆固醇的溶酶体积聚和固醇稳态反应的调节缺陷。NPC1和NPC2是细胞内胆固醇运输的关键参与者，并且是生产低密度脂蛋白胆固醇衍生的氧化甾醇所必需的。本文就NPC1和NPC2在胆固醇转运和胆固醇稳态调节中的作用进行综述。对鼻咽癌蛋白的研究将有助于进一步了解动脉粥样硬化发生的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cellular cholesterol homeostasis is maintained through activation of the designated sterol regulatory element binding proteins and liver X receptor transcriptional pathways. Insight into the molecular mechanisms that regulate these pathways has come from the study of Niemann-Pick C (NPC) disease. Mutations in the NPC1 and NPC2 disease genes lead to lysosomal accumulation of cholesterol and defects in regulation of sterol homeostatic responses. NPC1 and NPC2 are key participants in intracellular cholesterol trafficking and are required for production of low-density lipoprotein cholesterol-derived oxysterols. In this review, the function of NPC1 and NPC2 in sterol trafficking and regulation of cholesterol homeostasis is examined. Study of the NPC proteins will further understanding of the mechanisms involved in atherogenesis.