Indiana University scientists have solved a perplexing mystery regarding one of the body's main energy storage molecules, in the process shedding light on a possible route to treatment of a rare but deadly disease in teenagers.
The disease occurs when a genetic mutation causes excessive amounts of phosphate to build up in glycogen. Glycogen is a chain-like molecule the body uses to temporarily store glucose when it's not needed to provide energy for cellular activities. The excess phosphate causes unnatural glycogen structures to appear in the body, including the brain, resulting in progressive neurological problems.
In a paper in the March 2, 2011 issue of the journal Cell Metabolism, a research team led by Peter J. Roach, Ph.D., professor of biochemistry and molecular biology at the IU School of Medicine, has identified where the extra phosphate comes from, and how it is chemically linked to the glycogen molecules. The findings, Dr. Roach said, suggest a possibility for treating the disease stopping the body from producing glycogen.
Lafora disease, named after the Spanish physician who identified it, strikes early in the teen years with epileptic seizures and then other neurological symptoms that grow progressively worse. It is always fatal, usually within 10 years.
"It's a very harrowing disease and there's no treatment right now. It's thankfully rare, but for the families affected it's tragic," said Dr. Roach, Distinguished Professor and a Chancellor's Professor, Indiana University-Purdue University Indianapolis.
The disease is caused by a mutation to one of two genes, one leading to a defective version of a protein called laforin. In previous research, Dr. Roach and his collaborators showed that laforin's role is to remove phosphate residues from glycogen. When the body cannot produce laforin, the phosphate levels in glycogen build up, resulting in Lafora disease.
What had puzzled scient
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Indiana University School of Medicine