For beautiful ladies: a cure for Alzheimer's disease and obesity
Only for women
Alexandra Bruter, <url>
Investigating a potential cure for Alzheimer's disease, scientists from Atlanta found (Chan et al., Activation of Muscular TrkB by its Small Molecular Agonist 7,8-Dihydroxyflavone Sex-Dependent Regulates Energy Metabolism in Diet-Induced Obese Mice) that it also helps against obesity. However, only for women.
Neurotrophic growth factor (brain-derived neurotrophic factor, BDNF) has been discovered and investigated as a protein that controls the growth, development and maintenance of neurons. Since its discovery, a variety of studies have shown a link between BDNF and almost any diseases and conditions associated with nervous activity: Alzheimer's disease, Huntington's disease, Rett syndrome, schizophrenia, depression, anorexia and bulimia.
If a deficiency of one protein causes such serious consequences, it seems logical to try giving it to patients additionally and see if they recover. By itself, the BDNF protein, however, is not suitable for this role – it is unstable, quickly degrades in the body, and it would have to be taken a lot, often, and even in the form of injections – because almost any proteins, once in the stomach, are equated to food and partially split there. In particular, this is why insulin has to be administered subcutaneously, and not taken in the form of tablets.
Therefore, scientists began to look for another molecule that could perform the same functions as BDNF. Like many growth factors, BDNF is a receptor ligand located on the surface of cells that BDNF should convince to grow. One of the BDNF receptors is the TrkB receptor. TrkB is not only a receptor, but also a tyrosine kinase that phosphorylates itself.
Tyrosine kinases catalyze the addition of phosphate residues (phosphorylate) to the residues of the amino acid tyrosine in proteins. As a rule, this translates the protein from an inactive form to an active one. Such regulation provides a more fine–tuning than transcriptional - the protein can be activated exactly at the moment when the signal is received, and not wait until the RNA is synthesized, leaves the nucleus, enters the ribosome, and the protein is synthesized. In addition, the cell can inactivate the protein activated in this way, and not wait for it to fall apart and stop working.
Tyrosine kinases are very important enzymes because they regulate the growth and activity of so many systems in the body. For example, insulin receptors are also tyrosine kinases. The development of oncological diseases is associated with failures in their work, many tumor cells acquire mutant hyperactive tyrosine kinase on the way to success, and begin to grow especially quickly. Therefore, tyrosine kinase inhibitors are often offered as antitumor drugs (you can read about a tyrosine kinase inhibitor as a drug against leukemia in the essay "Fighting leukemia at the molecular level"). Oncological diseases are associated with excessive and uncontrolled cell proliferation, but many other diseases, especially those that overtake older people, are associated with the fact that old cells die quickly, and new ones replace them slowly or do not replace them at all. In this case, tyrosine kinases should not be inhibited, but they should be helped. Such cases include a drug against Alzheimer's, Huntington's, etc., simulating the effect of BDNF.
It turned out that it is possible to pick up a molecule more stable than BDNF, which has such a similar spatial structure that the TrkB receptor will not be able to distinguish them. The necessary substance was found in nature, in the leaves of the Godmania aesculifolia tree growing in Central and South America. This substance is 7,8–dihydroxyflavone (7,8-Dihydroxyflavone, 7,8-DHF), it can easily be synthesized artificially. In experiments with animals, it has shown good results in the fight against neurodegenerative diseases, strokes, mechanical damage to the brain, depression and some other diseases of the nervous system. Recently, its clinical trials as a drug against Alzheimer's disease have begun.
Even earlier, it was noticed that mice with missing or damaged genes encoding BDNF or TrkB have a tendency to overeat and obesity, and injections of BDNF into the brain, on the contrary, force animals to eat less and prevent them from gaining weight. Seriously, however, no one has investigated this phenomenon due to the inability to give animals the right amount of BDNF. And now its substitute has appeared – 7,8-DHF.
TrkB receptors are present not only on the surface of the cells of the nervous system, but also on the surface of muscle cells. Due to this, taking 7,8-DHF increased muscle metabolism and energy consumption in general. Female mice taking the drug tolerated a fat-rich diet without getting fat, they did not develop diabetes. In males, however, both obesity and metabolic changes characteristic of diabetes were observed.
The question remains open why this effect of 7,8-DHF is noticeable only in females (effects related to the nervous system are present in both sexes). Perhaps this is due to the mutual influence of estrogen and the BDNF signaling pathway. There is evidence in favor of the fact that 7,8-DHF affects the metabolism of estrogen, and estrogen enhances the signals transmitted along this pathway.
Portal "Eternal youth" http://vechnayamolodost.ru10.03.2015