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St. Jude Study Reveals a New Function for an Old Enzyme in Fatal Childhood Disease
Date:7/7/2008

A ubiquitous housekeeping enzyme has been found to play a major role in keeping the bone marrow environment healthy so it can nurture hematopoietic stem cells

MEMPHIS, Tenn., July 7 /PRNewswire-USNewswire/ -- The lack of a single protein usually thought of as a run-of-the-mill enzyme that helps to recycle molecules in cells causes an incurable and often fatal disease of children, according to St. Jude Children's Research Hospital investigators.

Children with this disease, called sialidosis, suffer from enlarged spleens and often develop vision problems, loss of coordination and seizures, among other symptoms. The patients generally die within the first few years of life.

St. Jude investigators showed in test tube experiments and mouse models of sialidosis that the loss of the protein NEU1 triggers a catastrophic falling of biochemical dominos that ultimately leads to disruption of normal formation of mature blood cells. A report on this work appears in the July 8, 2008, issue of the journal Developmental Cell.

"The discovery is important because it explains why patients with sialidosis have enlarged spleens and suggests that new drugs or gene therapies that target that problem might be an effective therapy," said Alessandra d'Azzo, Ph.D., a member in the St. Jude Department of Genetics and Tumor Cell Biology and the paper's senior author. "The results also explain how the loss of NEU1 can cause bone marrow transplantations to fail, and therefore suggests that such failures might also be corrected by target therapeutics."

The researchers showed that NEU1 controls how bags of digestive enzymes inside white blood cells, neutrophils and macrophages, discharge their contents into the bone marrow environment in a highly regulated process known as lysosomal exocytosis. These bags of enzymes, called lysosomes, rarely discharge their content outside of the cell. Instead, they use their enzymes inside the cell to digest no longer ne
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SOURCE St. Jude Children's Research Hospital
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