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Commonplace sugar compound silences seizures

ck thousands of years to Biblical times, when healers sometimes prescribed starvation as a potent way to fend off seizures.

UW-Madison researchers first began to investigate the role of sugar in controlling seizures after early experiments showed that children on sugar-free diets can rapidly experience seizures when they consume even a small dose of carbohydrates, such as a cookie or a little piece of bread.

But ketogenic regimens can be a miserable experience. "The kids can't eat any sugar at all. Imagine no bread or Christmas cake," says Roopra. But 2DG would work as an effective substitute because it enters cells and clogs up certain cellular enzymes. As a result, the body can't use its own glucose.

Though ketogenic diets seem to work in many epilepsy patients in whom existing treatments have been unsuccessful, scientists have struggled to understand the exact cellular connection between no sugar and no seizures. The UW-Madison work for the first time clears up some of that mystery.

Roopra has long explored how certain proteins known as "transcription factors" turn neuronal genes on or off. He has been particularly intrigued by one transcription factor known as NRSF, which is thought to control up to 1,800 genes in the brain, including many that are implicated in epilepsy. Like an electrical motherboard, NRSF ensures that neuronal genes switch "on" in the body's neurons, while remaining switched "off" in other regions where they normally play no role.

Roopra found that NRSF binds to another protein called CTBP. The finding "immediately raised alarm bells," Roopra says, because CTBP also binds to a free-floating molecule - NADH - that emerges when sugars break down in cells. To his surprise, Roopra found that CTBP binds to either NRSF or NADH. In other words, a cell with a lot of glucose generates a lot of NADH, so CTBP is more likely to bind with the sugar byproduct than NRSF. But without CTBP, NRSF most likely de
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Contact: Avtar Roopra
roopra@neurology.wisc.edu
608-265-9072
University of Wisconsin-Madison
15-Oct-2006


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