Niemann-Pick disease, type C and Roscoe Brady

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• 作者：Marc C. Patterson^a ; ^b ; ^{patterson.marc@mayo.edu} ; Steven U. Walkley^c ; ^{Steve.walkley@einstein.yu.edu}
• 关键词：Roscoe Brady ; Niemann-Pick disease ; Type C ; Cholesterol ; Oxysterols ; Gangliosides ; Biomarkers ; Filipin ; Cyclodextrin ; Miglustat
• 刊名：Molecular Genetics and Metabolism
• 出版年：2017
• 出版时间：January-February 2017
• 年：2017
• 卷：120
• 期：1-2
• 页码：34-37
• 全文大小：256 K
• 卷排序：120

文摘

The Niemann-Pick family of diseases was poorly understood until Roscoe Brady and his colleagues began their investigations in the 1960s. Following Brady's discovery of the defect in acid sphingomyelinase in Niemann-Pick disease, types A and B, Peter Pentchev, a senior scientist in the group, launched a series of investigations of an unusual lipid storage disease in a spontaneous mouse model. These led initially to identification of the cholesterol trafficking defect in the mouse, and then in human Niemann-Pick disease, type C (NPC). This discovery formed the basis of the standard diagnostic test for NPC for the next three decades. Subsequently, an international collaboration was established, based at the Brady lab at NIH, which culminated in discovery of the NPC1 gene. Roscoe Brady, Peter Pentchev and their colleagues defined and refined the clinical biochemical and pathological phenotypes of NPC in a series of elegant parallel studies. They also identified abnormal oxysterols in NPC; later work has proved such compounds to be sensitive biomarkers of the disease. The dedication of the Brady lab to NPC, and the discoveries that flowed therefrom, provided critical foundations for the current explosion of progress in this disease.