Sunday, December 12, 2010

Diabetes Drug Could Work Against Alzheimer’s Disease

If you are currently taking metformin (Glucophage, Diabetmin) for your diabetes, you will be glad to know that it might have the potential to also act against Alzheimer's disease.

Metformin is used by itself or combined with a sulphonylurea (Avandamet, Glucovance) or insulin to treat type 2 diabetes (also known as non-insulin-dependent diabetes mellitus)..How metformin helps control sugar in the blood is not fully understood. It has been postulated that metformin might potentiate the effect of insulin or that it might enhance the effect of insulin on the peripheral receptor site. This increased sensitivity seems to follow an increase in the number of insulin receptors on cell surface membranes. It is best taken after food to avoid stomach upset.

Scientists of the German Center for Neurodegenerative Diseases (DZNE), the University of Dundee and the Max-Planck-Institute for Molecular Genetics have found out that the diabetes drug metformin counteracts alterations of the cell structure protein Tau in mice nerve cells.

These alterations are a main cause of the Alzheimer's disease.

At the molecular level, Alzheimer's disease is characterized amongst others 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.

The investigators of the study carried out cell culture experiments with mouse nerve cells in their laboratories and found that the diabetes drug guards PP2A, a protein that is generally responsible for removing phosphate groups from the Tau protein.

By adding metformin to drinking water of the healthy mice, researchers found that mice who had the water witnessed a decrease in Tau-phoshorylation in brain cells.

To counteract this problem, researchers aimed at regulating the protein Protein phosphatase 2 (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 around Sybille Krauß and Susann Schweiger (University of Dundee) 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," says Krauß.

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 a next step, the scientists added metformin to drinking water of healthy mice. This also led to a reduction of Tau-phoshorylation in brain cells. In further experiments, the researchers now intend to investigate, whether metformin prevents the deposition of tau proteins also 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.

Continue to exercise and diet while taking your antidiabetic medication regularly.

Remember, medication is used in addition to, and not instead of lifestyle measures. These include:

  • Eat a healthy balanced diet. Basically, you should aim to eat a diet low in fat, high in fibre and with plenty of starchy foods, fruit and vegetables. CLICK HERE for guidance.
  • Lose weight if you are overweight. Getting to a perfect weight is unrealistic for many people. However, if you are obese or overweight then losing some weight will help to reduce your blood glucose level (and have other health benefits too).
  • Do some physical activity regularly. If you are able, a minimum of 30 minutes' brisk walking at least five times a week is advised. Anything more vigorous and more often is even better. For example, swimming, cycling, jogging, dancing. Ideally you should do an activity that gets you at least mildly out of breath and mildly sweaty. You can spread the activity over the day. Regular physical activity also reduces your risk of having a heart attack or stroke. CLICK HERE for details.

Journal Reference:

E. Kickstein, S. Krauss, P. Thornhill, D. Rutschow, R. Zeller, J. Sharkey, R. Williamson, M. Fuchs, A. Kohler, H. Glossmann, R. Schneider, C. Sutherland, S. Schweiger. Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proceedings of the National Academy of Sciences, Published online before print November 22, 2010

CLICK HERE for our other 21 posts on Alzheimer’s Disease

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