Researchers test sugary solution to Alzheimer’s

Feb 26, 2012

(Medical Xpress) -- Slowing or preventing the development of Alzheimer’s disease, a fatal brain condition expected to hit one in 85 people globally by 2050, may be as simple as ensuring a brain protein’s sugar levels are maintained.

That’s the conclusion seven researchers, including David Vocadlo, a Simon Fraser University chemistry professor and Canada Research Chair in Chemical Glycobiology, make in the latest issue of .

The journal has published the researchers’ latest paper Increasing O-GlcNAc slows neurodegeneration and stabilizes against aggregation.

Vocadlo and his colleagues describe how they’ve used an inhibitor they’ve chemically created — Thiamet-G — to stop O-GlcNAcase, a naturally occurring enzyme, from depleting the protein Tau of sugar molecules.

“The general thinking in science,” says Vocadlo, “is that Tau stabilizes structures in the brain called microtubules. They are kind of like highways inside cells that allow cells to move things around.”

Previous research has shown that the linkage of these sugar molecules to proteins, like Tau, in cells is essential. In fact, says Vocadlo, researchers have tried but failed to rear mice that don’t have these sugar molecules attached to proteins.

Vocadlo, an accomplished chess player in his spare time, is having great success checkmating troublesome enzymes with inhibitors he and his students are creating in the SFU chemistry department’s Laboratory of Chemical Glycobiology.

Research prior to Vocadlo’s has shown that clumps of Tau from an Alzheimer brain have almost none of this sugar attached to them, and O-GlcNAcase is the enzyme that is robbing them.

Such clumping is an early event in the development of Alzheimer’s and the number of clumps correlate with the disease’s severity.

Scott Yuzwa and Xiaoyang Shan, grad students in Vocadlo’s lab, found that Thiamet-G blocks O-GlcNAcase from removing sugars off Tau in mice that drank water with a daily dose of the inhibitor. Yuzwa and Shan are co-first authors on this paper.

The research team found that mice given the inhibitor had fewer clumps of Tau and maintained healthier brains.

“This work shows targeting the enzyme O-GlcNAcase with inhibitors is a new potential approach to treating Alzheimer’s,” says Vocadlo. “This is vital since to date there are no treatments to slow its progression.

“A lot of effort is needed to tackle this disease and different approaches should be pursued to maximize the chance of successfully fighting it. In the short term, we need to develop better inhibitors of the and test them in mice. Once we have better inhibitors, they can be clinically tested.

Explore further: Following a protein's travel inside cells is key to improving patient monitoring, drug development

More information: www.nature.com/nchembio/index.html , DOI:10.1038/nchembio.797

Provided by Simon Fraser University

4.7 /5 (10 votes)

Related Stories

New tool enhances view of muscles

Jan 23, 2012

Simon Fraser University associate professor James Wakeling is adding to the arsenal of increasingly sophisticated medical imaging tools with a new signal-processing method for viewing muscle activation details that have never ...

Recommended for you

New method to analyse how cancer cells die

15 hours ago

(Phys.org) —A team from The University of Manchester – part of the Manchester Cancer Research Centre - have found a new method to more efficiently manufacture a chemical used to monitor cancer cells.

The anti-inflammatory factory

Apr 22, 2014

Russian scientists, in collaboration with their colleagues from Pittsburgh University, have discovered how lipid mediators are produced. The relevant paper was published in Nature Chemistry. Lipid mediators are molecules that p ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Birger
not rated yet Feb 27, 2012
"expected to hit one in 85 people globally by 2050"

Spelling error... the proportion is MUCH larger than that. Indeed, research at Umeå University indicates that half of those born today will suffer some kind of dementia at high age.

"The research team found that mice given the inhibitor had fewer clumps of Tau and maintained healthier brains"

Mice engineered to express Alzheimer-like symptoms have genes from a small subset of humans. There is no guarantee that a cure will work beyond this subset.
Sorry to rain on your parade, but I don't want people to get unrealistic hope. This doesn not mean the research is unimportant -on the contrary all basic research is crucial to defeating this horrible disease.

More news stories

Computer program could help solve arson cases

Sifting through the chemical clues left behind by arson is delicate, time-consuming work, but University of Alberta researchers teaming with RCMP scientists in Canada, have found a way to speed the process.

Genetic code of the deadly tsetse fly unraveled

Mining the genome of the disease-transmitting tsetse fly, researchers have revealed the genetic adaptions that allow it to have such unique biology and transmit disease to both humans and animals.

Ocean microbes display remarkable genetic diversity

The smallest, most abundant marine microbe, Prochlorococcus, is a photosynthetic bacteria species essential to the marine ecosystem. An estimated billion billion billion of the single-cell creatures live i ...