Molecular Basis for Cystine Transport via Cystinosin (CTNS).

本研究项目旨在确定常染色体隐性遗传性溶酶体贮积症，胱氨酸病的分子基础。胱氨酸沉积症是由编码载体蛋白胱氨酸蛋白的CTNS基因突变引起的，该载体蛋白负责将胱氨酸转运出溶酶体区室。胱氨酸蛋白酶功能缺陷导致溶酶体内胱氨酸在所有身体细胞和器官中蓄积。肾脏最初在生命的第一年受到影响，通过近端肾小管损伤，随后是进行性肾小球损伤和终末期肾衰竭，如果不治疗的话，在儿童中期。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。白细胞胱氨酸测定是诊断和治疗监测疾病的基石。虽然有几种治疗方法可用于胱氨酸病，但尚无治愈性治疗方法。该提案旨在了解CTNS在溶酶体中功能的分子基础，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.