Molecular Basis for Cystine Transport via Cystinosin (CTNS).

本研究旨在确定常染色体隐性遗传性溶酶体储存障碍--胱氨酸病的分子基础。胱氨酸病是由编码载体蛋白胱氨酸蛋白的CTNS基因突变引起的，该蛋白负责将胱氨酸运出溶酶体隔室。半胱氨酸氨基转移酶功能缺陷会导致溶酶体内的胱氨酸在所有身体细胞和器官中积聚。肾脏最初在生命的第一年通过近端肾小管损伤，然后是进行性肾小球损伤，如果不治疗，在儿童中期会出现终末期肾功能衰竭。其他受影响的器官包括眼睛、甲状腺、胰腺、性腺、肌肉和中枢神经系统。白细胞半胱氨酸检测是疾病诊断和治疗监测的基石。尽管目前已有多种方法治疗胱氨酸病，但目前尚无根治性的治疗方法。这项建议试图了解CTNS在溶酶体中作用的分子基础，并为开发治疗这种疾病的新途径铺平道路。

This research project seeks to determine the molecular basis for the autosomal recessive lysosomal storage disorder, Cystinosis. Cystinosis is caused by mutations in the CTNS gene encoding the carrier protein cystinosin, responsible for transporting cystine out of the lysosomal compartment. Defective cystinosin function leads to intra-lysosomal cystine accumulation in all body cells and organs. The kidneys are initially affected during the first year of life through proximal tubular damage followed by progressive glomerular damage and end stage renal failure during mid-childhood if not treated. Other affected organs include eyes, thyroid, pancreas, gonads, muscles and CNS. Leucocyte cystine assay is the cornerstone for both diagnosis and therapeutic monitoring of the disease. Although several lines of treatment are available for cystinosis no curative treatment is yet available. This proposal seeks to understand the molecular basis for CTNS function in the lysosome and pave the way for developing novel routes to treat this disease.