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LSUHSC research discovery provides therapeutic target for ALS
Date:12/19/2012

New Orleans, LA Research led by Dr. Udai Pandey, Assistant Professor of Genetics at LSU Health Sciences Center New Orleans, has found that the ability of a protein made by a gene called FUS to bind to RNA is essential to the development of Amyotrophic Lateral Sclerosis (ALS). This discovery identifies a possible therapeutic target for the fatal neurological disease. The research will be available online in the Advanced Access section of the journal Human Molecular Genetics website, posted by December 21, 2012. It will be published in an upcoming issue of the journal.

The current project advances Dr. Pandey's ALS research by teasing out specifically how the FUS gene causes the disease. To find out whether or not the RNA binding ability of FUS was required for the disease pathogenesis, the researchers mutated FUS RNA binding sites and produced a version of FUS that couldn't bind RNA, both with and without ALS mutations. They found that not only could they eliminate FUS RNA binding, but when they blocked RNA binding, they also suppressed ALS related neurodegeneration, demonstrating that the RNA binding ability of FUS is essential to the ALS disease process.

The researchers are working with fruit flies the first animal model of FUS-related ALS, a model Dr. Pandey developed. The fruit flies were engineered to carry and express a mutated human FUS gene. This mutated FUS gene has been shown to be one of the causes of both familial and sporadic ALS. In the fruit flies, the resulting neurodegeneration impairs their ability to walk or climb and the defect is also easily visualized in the structure of their eyes. In addition, the flies carrying the defective FUS gene demonstrate hallmarks of the human disease, such as an age-dependent degeneration of neurons, accumulation of abnormal proteins and a decrease in life span. The fly model is a valuable resource for performing drug screens to identify drugs that could modify the effects of the mutated gene
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Contact: Leslie Capo
lcapo@lsuhsc.edu
504-568-4806
Louisiana State University Health Sciences Center
Source:Eurekalert

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