Biologist Vladimir Muronetz: What is the cause of neurodegenerative diseases

What is the cause of neurodegenerative diseases? What role to humans play the chaperones? What are the different approaches to the treatment of Alzheimer's disease and mad cow disease? This information tells the doctor of biological Sciences Vladimir Muronetz. Quite a lot of neurodegenerative diseases are called amyloid diseases or conformational diseases. Their essence lies in the fact that in the cells surrounding nerve cells, fall of amyloid aggregates is the aggregates of proteins that have a specific structure. For a long time it was thought that because of the emergence of these units and experiencing these diseases. Sometimes they are also called conformation, because it is bound to proteins.

Of course, if we have in some protein mutation occurs or a change in the structure due to modification, for example chemical, these proteins change their conformation, and start to form aggregates. The frequent case is the so-called freonovye of the disease when infectious protein called a prion ― is attached to the native prion protein, native protein, changing its conformation, also turns in an infectious protein, and then formed aggregates.

Diseases such quite a lot, but I will mention only two. First, it Alzheimer's disease is arguably the most unpleasant disease, because it hurts a lot of people, tens of millions, especially in developed countries; as life expectancy increases, such patients become very much. Somewhere near half of the people who reach the age of 90, was developing Alzheimer's disease. This requires a very large cost because these people can not be left alone all the time necessary to take care of them, they sometimes even suicidal. In addition, the illness itself is very unpleasant, because they are physically the same person you knew, and because of the fact that he doesn't remember, doesn't recognize you and behaves inappropriately, it is a big problem for the family.

In the world there are many institutions, many laboratories going to the conference 5-10 thousand people associated with the study of this disease. The molecular mechanisms are almost completely known, but no medication is still there, just a bit removed symptoms.

The second disease is also amyloid, too, conformational disease, which made a lot of noise about 10-15 years ago, when he appeared. They began to talk about this disease like mad cow disease, or scientifically it is called spongiform encephalopathy of cattle. In humans, the disease practically does not occur, there are hereditary forms, but this rare cases, a few cases in the whole of Russia a year. And infectious the disease is, but ill people usually 10-15 years, because the very long incubation period.

To compare, of course, Alzheimer's disease and freonovye disease incidence or cost is impossible, but it's very frustrating: today ate some infected meat, and in 10-15 years ill strange disease. I remember in those years, when all the Newspapers wrote about it, even the old 90-year-old has stopped eating meat. This disease is slightly different because there is a prion that transmits the disease. Here too almost all is known about this disease but how to prevent this disease is still not know.

15 years ago, it has been suggested that treating these illnesses by using the so-called chaperones.

Chaperones opened a long time ago — in the beginning 90-x years and even earlier. Proteins that help other proteins to fold correctly, or not allowed to aggregate with each other. The name comes from the French word: this is Bonn, which was accompanied by girls in the society so that nothing bad happens to them. Approximately the same function, is believed to perform chaperones: proteins that are not aggregated, not changed, etc.

If amyloid diseases are associated with those that are formed very large aggregates Moshe humans or animals, it is clear that if we have chaperones, they can be chopped into small pieces these machines, and the disease will disappear. Assumed that will begin to enter the chaperones in the brain, although this is not an easy task, you could even transgenic animals, in principle, for such a noble task to create.

It turned out that all is not so simple. Around the same time, it became clear that such large aggregates, which are in the brain, there is nothing particularly wrong doing, as dangerous as small aggregates, called oligomers of prions or beta amyloid, which causes Alzheimer's disease. They are dangerous and cause cell death. So if we cut it into small pieces of units, it will be even worse. And it became clear that hardly with the help of chaperones can be cured.

Information on the action of chaperones have been very controversial, because one thought that they destroy the units, others thought that they, on the contrary, make good the bad amyloid protein aggregates. This was due to the fact that used chaperones from different sources. For example, watching will influence chaperones isolated from cells of microorganisms, prions, in the brain of animals. It is clear that they should meet in the brain, these two proteins. Gradually it became clear that everything depends not only from the fact that there is a chaperone, a modified protein conformational and aggregation from their interaction, and everything connected with the order in which conformation, the condition of the chaperone is.

If you have this protein in the cell in the active state, if it has a sufficient amount of energy — it needs energy, adenosine triphosphate — in order to function, it's all good, nothing wrong it with either the prion or with beta-amyloid does not. But if he is somehow tainted, premodification, for example, by oxidation of some proteins, there may be special forms of these proteins, they are connected to chaperone and ruin it. As in the two-cylinder engine, if one cylinder is blocked, the second seems to be normal, but work as it should not. The same happens with the chaperones.

Good, functionally active chaperones nothing wrong with prion and other amyloid proteins do not. On the contrary, can even prevent their aggregation. And if the chaperone is a little spoiled, when it is joined even good pionowy protein with unmodified conformation, he then may purchase the wrong conformation, and it can gather fibrils, bad units, etc. is Important not just to give the additional proteins as chaperones in the brain of animals or humans, and it is necessary that this system worked well. It's much easier than to create transgenic animals or attempt to enter any proteins in the brain. Therefore, it is sufficient, as already known, to drink a good oxidant, to avoid any misfolded proteins, giving a lot of energy so they can function, and then all will be well with prions. Most importantly, the chaperones keep in good condition. We are talking about the chaperones that exist in all cells. I previously mentioned that there are chaperones of microorganisms and maybe they play a little different role in the infection of animals, especially in the case pionowych proteins.

The fact that the mad cow infection occurs if a person eats poorly processed meat of a sick animal, even if it's well done, and prions can get first in the gastrointestinal tract, then into the human brain and cause the disease. The probability of such a process is small, the disease occurs rarely, even when eating infectious prions, but nevertheless it happens.

How the process of penetration of the infectious prions in the brain, not really known. It is possible that a role played by the microorganisms that live in the gastrointestinal tract. Because they are the best chaperones of microorganisms and if the cells are destroyed constantly exposed to autolysis, then these chaperones may go to the gastrointestinal tract and there meet with prions. It has been shown that if these chaperones will meet with the prion protein, they, first, will lead them into an even more pronounced amyloid condition and will make small particles of several nanometers size, which would be easier to penetrate through the intestinal wall. It is possible that in the infected human an important role, those microorganisms that live with us in the gastro-intestinal tract, a lot of them, they can be different, and chaperones, they may be different. Therefore, depending on the microflora, infection may occur or not occur.

The main problem that now arises in the study of amyloid diseases lies in the fact that it is necessary to find such connections, which will be this amyloid to prevent aggregation. Such compounds are, they can be found even in well-known drugs, not even drugs, just the spices-for example turmeric — it's pretty well prevents the aggregation of proteins. There is a junction with an even more pronounced anti-aggregating effect, antiplatelet agents. It is quite possible that it will be possible to find some connection that will prevent this aggregation to translate, for example, these forms in very large units, stimulating aggregation, preventing thus cell killing.published



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