Researchers testing sugary Alzheimer’s solution
Slowing or preventing Alzheimer’s disease may be as simple as maintaining a particular protein’s sugar levels, according to a new study co-authored by SFU chemistry professor David Vocadlo in the latest issue of Nature Chemical Biology.
The researchers used an inhibitor they chemically created to block the enzyme O-GlcNAcase from depleting Tau proteins, which are abundant in the brain, of essential sugar molecules.
Tau stabilizes structures in the brain called microtubules, which “are kind of like highways inside cells that allow cells to move things around,” says Vocadlo, a Canada Research Chair in chemical glycobiology.
Previous research has shown that the linkage of sugar molecules to Tau and other proteins is essential. In fact, says Vocadlo, researchers have tried but failed to rear mice that don’t have these sugar molecules attached to proteins. Previous research also showed that clumps of Tau from an Alzheimer’s 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.
Vocadlo’s grad students Scott Yuzwa and Xiaoyang Shan found that when given to mice the researchers’ inhibitor, Thiamet-G, blocks O-GlcNAcase from removing the sugars off Tau. The mice also had fewer clumps of Tau and maintained healthier brains.
“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.”