Article Text

  1. M. Meislin,
  2. R. Heidenreich
  1. Department of Pediatrics, University of Arizona College of Medicine, Tucson, AZ


Niemann-Pick type C (NPC) is an autosomal recessive disease that affects children at a young age with hepatosplenomegaly and neurodegeneration that ultimately leads to mortality. The disease is due to a mutation in the NPC1 protein that leads to the intracellular accumulation of cholesterol within the cell due to a disruption in unesterified cholesterol trafficking. The specifics of how mutations in NPC1 cells inhibit the cholesterol movement pathway are still yet to be explained, but previous research suggests that intracellular movement of cholesterol-rich lipid rafts may be involved. To understand better the nature and role of these rafts, proteomic analysis will identify proteins important in the structures and function of these domains. The importance of this research is to not only perfect the protein extraction and 2-D gel electrophoresis but to start the preliminary steps in analyzing the difference in proteins present in NPC normal, NPC carriers, and NPC mutants, which will give possible candidates involved in cholesterol trafficking and an hypothesis of the cholesterol trafficking pathway. The perfected techniques of 2-D gel electrophoresis produced gels for wild-type, carrier, and mutant of NPC1 protein. These three gels showed distinct similarities and differences. The similarities were depicted to show consistency within the gels that demonstrate not only successful gel runs but proteins that are continually not affected by NPC. The differences showed either positive or inverse relationships with the expression of NPC1; these proteins are candidates for possible further research since they show a correlation to the expression of NPC1 and may be involved in the cholesterol trafficking pathway. The next step is to identify the proteins that are changed by NPC1 expression, and through further experimentation with Sypro staining and computer analysis—which has recently begun—will give insight into these proteins and ultimately the pathway of cholesterol trafficking. The current results have given a stepping stone in focusing on a successful protocol that has given evidence of other possible proteins that are affected by NPC1 and create the devastating NPC disease.

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