Methylene blue inactivates molecular residues that promote bonding of tau proteins

Helmholtz Association of German Research CentresFeb 21 2013

The study published in "Angewandte Chemie" might help to work out strategies for developing potential drugs. As the team of scientist including Markus Zweckstetter and Eckhard Mandelkow report, methylene blue inactivates molecular residues that promote the bonding of tau proteins.

Methylene blue is a multi-talented substance with a long history. The synthetic compound was first produced in 1876, and since then has served not only as a blue dye, but also as a medical drug - for example to treat malaria and prevent urinary tract infections. It is now also being debated as a potential treatment for Alzheimer's disease.

Methylene blue works in many ways. With regard to Alzheimer's, it is interesting to note that it prevents the clumping of "tau proteins". Such aggregates are typical in numerous forms of dementia: The protein clumps accumulate in the brain cells, disrupt their function, and can even kill them.

"Tau proteins are actually extremely important, because they stabilize the transport routes inside each nerve cell," explains Prof. Eckhard Mandelkow, who works at the German Center for Neurodegenerative Diseases (DZNE) and the caesar research center in Bonn. "However, in cases of Alzheimer's, they stop doing their job. The transport routes inside the cells break down, and supplies essential for the survival of the cells can no longer reach their destination. In addition, the tau proteins stick together. These aggregates are also harmful and are a typical characteristic of the disease."

Such characteristics can be reproduced in animal studies. Previously, another team of scientists led by Dr. Eva-Maria Mandelkow was able to prove that methylene blue is able to alleviate the symptoms of an illness in mice and threadworms. However, no significant data from human patients has been collected so far. Furthermore, to date it was unknown, why methylene blue had the observed effect. "Methylene blue inhibits the aggregation process," Eckhard Mandelkow emphasizes. "But the way in which this happens was unknown until now."

The study now published in "Angewandte Chemie" reveals the nature of this process: Markus Zweckstetter's research group at the DZNE site in G-ttingen and the Max Planck Institute for Biophysical Chemistry in G-ttingen in collaboration with the Mandelkow team have been able to prove that methylene blue deactivates molecular residues which promote the bonding of tau proteins. Moreover, the researchers found indications that the substance acts as a spacer to keep the proteins apart. These findings could lead to the development of modified forms of methylene blue and new types of treatment.