TAILIEUCHUNG - Báo cáo khoa học: Hydrophilic iminosugar active-site-specific chaperones increase residual glucocerebrosidase activity in fibroblasts from Gaucher patients

Gaucher disease is an autosomal recessive lysosomal storage disorder caused by the deficient activity of glucocerebrosidase. Accumulation of glucosylceramide, primarily in the lysosomes of cells of the reticuloendo-thelial system, leads to hepatosplenomegaly, anemia and skeletal lesions in type I disease, and neurologic manifestations in types II and III disease. | ễFEBS Journal Hydrophilic iminosugar active-site-specific chaperones increase residual glucocerebrosidase activity in fibroblasts from Gaucher patients Hui-Hwa Chang1 Naoki Asano2 Satoshi Ishii1 3 Yoshitaka Ichikawa4 and Jian-Qiang Fan1 1 Department of Human Genetics Mount Sinai Schoolof Medicine New York NY USA 2 Department of Pharmacology Hokuriku University Kanazawa Japan 3 Department of Agriculturaland Life Sciences Obihiro University of Agriculture and Veterinary Medicine Japan 4 Department of Pharmacology The Johns Hopkins Schoolof Medicine Baltimore MD USA Keywords active-site-specific chaperone drug design Gaucher disease glucocerebrosidase isofagomine Correspondence . Fan Department of Human Genetics Mount Sinai School of Medicine Fifth Avenue at 100th Street New York NY 10029 USA Fax 1 212 849 2508 E-mail Received 14 March 2006 revised 14 April 2006 accepted 10 July 2006 doi Gaucher disease is an autosomal recessive lysosomal storage disorder caused by the deficient activity of glucocerebrosidase. Accumulation of glucosylceramide primarily in the lysosomes of cells of the reticuloendothelial system leads to hepatosplenomegaly anemia and skeletal lesions in type I disease and neurologic manifestations in types II and III disease. We report herein the identification of hydrophilic active-site-specific chaperones that are capable of increasing glucocerebrosidase activity in the cultured fibroblasts of Gaucher patients. Screening of a variety of natural and synthetic alkaloid compounds showed isofagomine N-dodecyl deoxynojiri-mycin calystegines A3 B1 B2 and Cl and 1 5-dideoxy-1 5-iminoxylitol to be potent inhibitors of glucocerebrosidase. Among them isofagomine was the most potent inhibitor of glucocerebrosidase in vitro and the most effective active-site-specific chaperone capable of increasing residual gluco-cerebrosidase activity in fibroblasts established from Gaucher patients with the most .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• oxidation
• chemical reaction
• tumor cells
• medical knowledge
• medical research
• analysis of cytoplasmic
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• gastric cancer
• hormone medicine
• biochemical studies
• environmental medicine