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Researchers decipher modus operandi of potential Alzheimer's drug
Date:2/20/2013

s 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 Gttingen and the Max Planck Institute for Biophysical Chemistry in Gttingen 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.

Background:

Methylene blue tackles sulphur groups

NMR spectroscopy, a powerful technique for investigating biomolecules, was centrally important to the current study. "We found that methylene blue reacts with certain elements in the tau proteins called cysteines," Prof. Zweckstetter summarizes.

This reaction is highly effective. Methylene blue specifically modifies the tau proteins at critical spots: Of the up to 441 elements which a tau protein can consist of particularly the two cysteines are modified. The elements directly modified are the so-called SH groups, molecular appendages comprising sulphur and hydrogen which are typical of cysteines. Oxygen atoms now couple with them.

"This chemical transformation prevents tau proteins from bonding together," says Zweckstetter. "Otherwise SH groups from different proteins would react and form a so-called disulfide bridge. Now, this is no longer possible, because the reaction with methylene blue eliminates the SH groups."

In a healthy organism, the formation of these disulfide bridges is suppressed naturally. "The cell
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Contact: Dirk Frger
presse@dzne.de
49-228-433-02260
Helmholtz Association of German Research Centres
Source:Eurekalert

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