Methylene blue, the famous chemical dye and reagent, is now a candidate for the role of a new drug against Alzheimer's disease.
The substance, as it turned out, can modify the structure of tau proteins that accumulate in the brain with this disease.
Researchers from Gottingen and Bonn recently shed some light on this molecular process.
Their work, published in the German edition of Angewandte Chemie, can help in the development of new drugs. A team of scientists, led by Marcus Zweckstetter and Eckhard Mandelkau, reported that methylene blue inactivates the molecular structure that is responsible for the adhesion of tau proteins.
Methylene blue is generally a very useful and universal substance with a long and glorious history. This synthetic dye was first synthesized in 1876. Since then, it has not only been used as a blue dye, but also managed to be in the role of a medicine for malaria and urethritis. In post-Soviet countries, it is still used today to treat purulent-inflammatory skin diseases. Now they are predicting the role of a new drug against the incurable Alzheimer's disease.
Tau proteins are unique proteins, accumulations of which are found in the brain in many forms of dementia. These proteins are deposited in nerve cells, disrupt their function, and even lead to their death. Over the years, such a process, called neurodegeneration, leads to loss of nerve function, worsening of thinking, impaired control of the body.
"Tau proteins are extremely important, because they stabilize transport routes inside each nerve cell. However, in Alzheimer's disease, they stop performing their functions. Transport channels in neurons are destroyed, cell-important substances do not reach their destination. And the tau proteins themselves begin to "stick together", forming clusters, which we find in the analyzes, "explains Professor Eckhard Mandelkau, who is working on this issue at the German Center for Neurodegenerative Diseases (DZNE).
These characteristics of the disease can be reproduced in animal experiments. Before that, another team of scientists, led by Dr. Eva-Maria Mandelkau, was able to prove that methylene blue alleviates the symptoms of the disease in mice. However, as long as there is not enough evidence on the effectiveness of the drug in humans.
Until today, it was not clear why methylene blue has such an effect. Only recently it was found that it affects the process of "sticking" of cysteine ??protein residues.
NMR spectroscopy, a powerful method for studying biomolecules, played a very important role in the study of German scientists. Professor Tsokkstetter says that scientists have established that methylene blue interacts with sulfhydryl (SH) amino acid groups of cysteine, which is part of tau proteins.
This reaction is very effective. Methylene blue specifically modifies tau proteins at critical points. Of the 441 amino acid residues that make up the protein, methylene blue binds only 2 cysteine ??residues.
As a result of the reaction, the sulfhydryl groups can not form disulfide bridges, cross-linking parts of the protein.
There are other substances, besides methylene blue, which can suppress the aggregation of tau proteins. Some of them act differently, preventing the formation of beta-sheets of protein. Scientists believe that effective treatment of Alzheimer's disease will require the use of a combination of different substances.
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