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Research reveals lipids' unexpected role in triggering death of brain cells
Date:11/12/2009

The lipid that accumulates in brain cells of individuals with an inherited enzyme disorder also drives the cell death that is a hallmark of the disease, according to new research led by St. Jude Children's Research Hospital investigators.

The work provides the first evidence that a lipid can initiate the suicidal, or apoptotic, response in cells. The findings involve a lipid called GM1-ganglioside. Lipids are fat-like molecules. GM1 builds up with devastating results in the brain cells of patients with GM1-gangliosidosis because they lack the enzyme required to break down that molecule.

Working in mice missing this key enzyme, researchers reported new details of how GM1 accumulation inside certain structures in brain cells disrupts their internal calcium balance. This imbalance ultimately leads to the programmed cell death known as apoptosis. The work appears in the November 13 online edition of Molecular Cell.

"The finding is essential for understanding the causes of progressive loss of brain cells, characteristic of this disease," said Alessandra d'Azzo, Ph.D., of St. Jude Genetics and Tumor Cell Biology. She is the senior author of the report and holds the Jewelers for Children Endowed Chair in Genetics and Gene Therapy. The work also provides hints for a strategy to intervene in the disease process.

The research led d'Azzo and her colleagues to propose that the death of brain cells and neurodegeneration that strikes GM1-gangliosidosis patients is a two-step process. The investigators demonstrated that blocking the first step in this process prevented cells from self-destructing, which was not the case when just the second step was inhibited. They predicted the discovery might have important implications for developing new treatments for this catastrophic disease.

The findings also have implications for scientists studying other aspects of the cross-talk between intracellular compartments, involving calci
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Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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