Diabetes drug shows promise in controlling Alzheimer's
By Ernest Gill (China Daily)
Updated: 2010-12-15 09:36
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A common medication used in type 2 diabetes might have the potential to also act against Alzheimer's disease.
This is the result of a study by scientists of the German Center for Neurodegenerative Diseases (DZNE) in Bonn, the University of Dundee and the Max Planck Institute for Molecular Genetics in Berlin.
The researchers found that the diabetes drug metformin counteracts alterations of the cell structure of tau protein in mice nerve cells. These alterations are a main cause of Alzheimer's disease. They also uncovered the molecular mechanism of metformin in this process.
"If we can confirm that metformin also shows an effect in humans, it is certainly a good candidate for an effective therapy on Alzheimer's disease," says Sybille Krauss from DZNE.
Alzheimer's disease is a form of dementia that affects almost exclusively elderly people. Neurons in their brains die, leading to cognitive impairment.
At the molecular level, the disease is characterized amongst other things by the formation of tau protein deposits in nerve cells. Tau is a molecule that usually binds to the supportive cytoskeleton and performs a function in the transport system of the cell.
In Alzheimer's disease, tau is tipped too strongly with phosphate groups. This phosphorylation causes removal of tau from the cytoskeleton and aggregation.
To counteract this problem, researchers targeted the regulation of the protein PP2A. This protein is normally responsible for removing phosphate groups from tau protein. In Alzheimer's disease, PP2A is not active enough - leading to an increased phosphorylation and deposition of tau.
The scientists led by Krauss, therefore, looked for a drug that increases the activity of PP2A. "So far there is no drug on the market that targets the formation of tau aggregates," Krauss says.
In cell culture experiments with mouse nerve cells, the researchers showed that metformin directly protects PP2A against degradation by preventing the binding to special degradation proteins. This mechanism of metformin has been unknown so far.
In addition, an increase in PP2A activity leads to a reduction in tau phosphorylation.
In an additional step, the scientists added metformin to the drinking water of healthy mice. This also led to a reduction of tau-phosphorylation in brain cells.
In further experiments, the researchers now intend to investigate whether metformin also prevents the decomposition of tau proteins in mouse models of Alzheimer's disease and improves cognitive performance of the animals.
The effect in humans will then be tested in clinical studies. There is no risk of unexpected side effects, due to the fact that the drug is already used against diabetes.