We've reported on numerous different approaches by scientists looking to tackle Alzheimer's disease. While some, such as the anticancer drug bexarotene and a compound known as J147, show great promise, there is still no approved treatment to slow the disease's progression. The latest promising candidate for a treatment comes from Canada's Simon Fraser University (SFU), where a team has concluded that ensuring that sugar levels in a brain protein known as tau are maintained could slow or prevent the fatal disease.
Tau proteins are abundant in neurons of the central nervous system where they stabilize microtubules, which act like highways inside cells that allow intracellular transport. Previous research has shown that defective tau proteins can lead to Alzheimer's disease and that linkage of sugar molecules to proteins like tau is essential in cells.
Previous research has also shown a naturally occurring enzyme known as O-GlcNAcase robs tau of these essential sugar molecules, resulting in an Alzheimer brain having clumps of tau have almost none of this sugar attached to them. This clumping is an early sign of the disease and the number of clumps correlates with its severity.
Using a chemically-created inhibitor called Thiamet-G, SFU chemistry professor David Vocadlo and his colleagues have been able to stop O-GlcNAcase from depleting tau proteins of sugar molecules. The researchers found that mice given a daily dose of Thiamet-G in their drinking water had fewer clumps of tau and maintained healthier brains.
"A lot of effort is needed to tackle this disease and different approaches should be pursued to maximize the chance of successfully fighting it," said Vocadlo. "In the short term, we need to develop better inhibitors of the enzyme and test them in mice. Once we have better inhibitors, they can be clinically tested."
The team's paper, "Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation," is published in the journal Nature Chemical Biology.
Source: Simon Fraser University
See the stories that matter in your inbox every morning