14 February 2020
Russian molecular biologists and mathematicians have calculated a formula for a short protein molecule, capable of suppressing many forms of clinical depression without causing serious side effects, says Skolkovo Science and Technology Institute (Skoltech) press service.
“This peptide discovery is a very exciting result. Now, pre-clinical testing is needed and we expect a lot to come from it,” Skoltech researcher Dmitry Karlov said.
Fighting chronic depression is complicated, because the neurophysiologists do not completely understand the nature of this illness. For instance, the scientists have not yet discovered which brain parts exactly work wrong, and whether depression is a purely genetic disease. This is why in one third of all cases taking anti-depressants either has no effect or makes the problems worse, causing serious side effects. All this forces the scientists to look for genes related to development of depression and new drugs, capable of effectively fighting it.
The scientists from Skoltech, Moscow State University, Sechenov Institute of Evolutionary Physiology and Biochemistry and Institute of Physiologically Active Substances have discovered a potential solution by studying the behavior of various protein molecules, capable of interacting with the so-called NMDA receptors.
Disruption of functioning of these receptors is believed to be one of the main reasons for development of many forms of chronic depression that cannot be fought using the existing drugs. Some substances, such as ketamine, can suppress the NMDA-receptors and remove some depression symptoms, but they also have a lot of dangerous side effects.
Karlov and his colleagues have picked a safe replacement for those substances by using the Zhores supercomputer installed in Skoltech last January, as well as artificial intelligence systems, capable of finding analogues of already existing molecules. Using these algorithms, the scientists have discovered that a short protein chain of two amino acids – D-Phenylalanine and L-Tyrosine – has very similar properties to Ifenprodil, one of the NMDA-receptor inhibitors.
After developing several versions of this peptide, the scientists have synthesized small amounts of this substance and tested it, using rat brains slices and neuron liquid solution.
These experiments confirmed that the new proteins have actually bonded with NMDA receptors and inhibited them. In the upcoming days, the biologists plan to determine the most promising version of this molecule during live tests on rodents suffering from chronic depression.Print
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