Protein clumping, dementia and death
Dementia and paralysis explained by protein puzzleAlexey Tymoshenko, GZT.RU
Scientists from Barcelona have found one of the causes of the disease that paralyzed the famous astrophysicist Stephen Hawking and which leads to the death of most patients.
Amyotrophic lateral sclerosis and a number of other diseases are associated with the fact that protein molecules come together in toxic complexes.
In the journal PLoS Computational Biology, Spanish researchers published an article describing the results of their calculations. By constructing a mathematical model of the interaction of protein molecules, scientists were able to demonstrate how ordinary proteins turn into highly toxic and cell-killing clots.
Sticking together, dementia and death
Amyotrophic lateral sclerosis, a rare and dangerous disease, has become widely known thanks to the most famous patient – astrophysicist Stephen Hawking.
The scientist was diagnosed at the age of 22, and soon he was almost completely paralyzed, and his speech was hardly understood by close relatives. A few years later, Hawking was supposed to die, but contrary to all forecasts, he survived and was even able to visit weightlessness, write several popular books, establish that black holes can evaporate and receive the highest award of the United States for civilians, despite his British citizenship.
But most patients with amyotrophic sclerosis die within a few years. The nerve cells of the brain responsible for muscle movement die off in them, and as a result, the respiratory muscles stop contracting. Moreover, during the development of the disease, characteristic plaques are found in dying cells, resembling those that are formed in other diseases.
Similar phenomena, in particular, are observed in Alzheimer's and Parkinson's diseases. With them, microscopic examination of nerve cells reveals clumped protein complexes that eventually lead to the death of neurons, and already the death of neurons is manifested by various symptoms – from senile dementia in Alzheimer's disease to impaired coordination of movements in Parkinsonism.
If it were possible to understand how proteins begin to stick together and why this happens, a number of dangerous diseases could, if not cured, then at least significantly slow down their development.
It should be emphasized: amyotrophic lateral sclerosis and Alzheimer's disease may have different root causes. But they have a common place in the form of the formation of protein plaques, and this is what molecular biologists have studied.
From computers to medicines
In order to reveal in detail the process of protein adhesion, scientists had to use the achievements of seemingly distant sciences from medicine. First of all, most of the research took place not with test tubes, but with computer models, because it is not so easy to look at individual molecules in the process of interaction, especially if you have to check a lot of different options.
Knowing how the clumping proteins are arranged, scientists were able to simulate their connection into groups (clusters) at different angles and in different combinations, and also checked what would happen when their structure changed. The time spent on carrying out such work in test tubes cannot even be estimated, but the time of a computer experiment is determined only by computing power.
From mutation to disease
As scientists have found out, normally proteins also stick together – but in pairs. Each of them has a special "sticky" area, which differs from all the others in that another molecule can join it, and normally the proteins stick together so that the "sticky" fragments completely cover each other. In fact, it resembles a puzzle or a children's constructor: one detail exactly matches the other, and nothing superfluous remains on the side.
But if an error (mutation) creeps into the genes encoding the structure of these proteins, then the molecules will stop sticking together in pairs. More precisely, they will stick together incorrectly: leaving "sticky" areas outside. On which, in turn, other molecules will "stick", and so on until a toxic plaque forms. The plaque will cause malfunction and cell death, and cell death will lead to the development of the disease.
Now, with the knowledge of this mechanism, scientists can try to either restore the normal form of proteins, or learn to selectively block the adhesion of the "wrong" protein. Medicines for this have yet to be developed, but at least they will not have to be searched blindly.
Portal "Eternal youth" http://vechnayamolodost.ru18.09.2009