Demethylation will cure Alzheimer's
Has a cure for Alzheimer's disease been found?
Alexey Aleksenko, Forbes, 24.01.2019
Researchers from the University of New York at Buffalo have discovered a way to restore brain functions in experimental animals that were disrupted due to Alzheimer's disease.
It is probably premature to call this scientific work sensational, but it cannot be ruled out that it is on its basis that a therapy will be developed that can reverse the development of neurological symptoms in Alzheimer's disease. Until today, such a result was never even dreamed of: the maximum that drug developers could count on was to stop or at least slow down the development of the disease at an early stage. However, a team of researchers of Chinese origin, most of whom work at the State University of New York in Buffalo, came up with a much more ambitious task. They observed in the experimental rodents almost complete – albeit temporary – recovery of cognitive functions. The key to success turned out to be interference with epigenetic mechanisms – chemical labels on chromosomes that regulate the work of genes.
It was known that in Alzheimer's disease, the work of a certain class of receptors in the brain is disrupted. Neuronal receptors respond to neurotransmitter substances, of which dopamine is probably the most famous. But in this case we are talking about the less popular and probably the least studied of neurotransmitters – glutamate. Almost half of all neurons in the brain are able to respond to glutamate because they contain the corresponding receptor proteins. When glutamate molecules appear, the neuron is excited and transmits a nerve impulse; this is the mechanism of action of the neurotransmitter.
Glutamate is an indispensable component of most food products, and this substance is even added artificially to the composition of many food concentrates. Glutamate gives food a characteristic "meat" (or "protein") taste. Usually, glutamate consumed as part of food enters the bloodstream, but does not reach the brain, because it is not able to pass through the blood-brain barrier. However, a very large amount of glutamate eaten can still affect consciousness, causing a slight excitement comparable to the effect of one cup of coffee.
In Alzheimer's disease, the work of glutamate receptors is disrupted. It could be assumed that this is due to a disorder in the regulation of the corresponding genes. It was found out that in the brain cells of patients suffering from Alzheimer's disease, the chromosomal structure was changed, including in the region of glutamate receptor genes.
The work of human genes depends on how exactly the DNA is stacked in the chromosome around protein molecules – histones. In particular, in the histone H3 molecule at the very beginning of the protein chain there is an amino acid lysine, to which a chemical group, methyl, is sometimes attached. Methylated histone begins to behave differently, shifting the DNA chain differently and turning off those genes that will be in this area. This mechanism is part of a broad class of regulatory cascades known as "epigenetics".
Epigenetic changes – increased methylation of histones – were observed in brain cells, namely in the prefrontal cortex, in Alzheimer's patients, as well as in laboratory mice simulating the development of this human disease.
Researchers from Buffalo suggested that if the cell is prevented from methylating histones, gene activity will be restored, glutamate receptors will return to operation, and neurological symptoms of Alzheimer's disease will be alleviated. All this can be done with the help of chemical compounds that block special enzymes (euchromatin histone methyltransferases 1 and 2). When mice were injected with inhibitors of these enzymes, an amazing effect was observed: short-term memory and other cognitive functions in rodents recovered almost to their original level.
The effect of the drug administration did not last long, about a week. However, there is no reason why the drug cannot be used on a regular basis. In addition, the administration of the drug had no effect on amyloid plaques, one of the most important signs of Alzheimer's disease, acting at a different level of regulation.
In the last part of the article, the authors note that Alzheimer's disease is most likely not limited to a malfunction of glutamate receptor genes – many factors are involved in this disease, many of which have not yet been studied. On the other hand, manipulations with epigenetic mechanisms inevitably affect a wide range of genes. If epigenetics really lies at the root of Alzheimer's disease, the approach of researchers from Buffalo may allow to simultaneously normalize the work of many cellular systems. It may be possible to develop a therapy that not only stops the development of the disease, but also removes all its terrible consequences for the cognitive function and social activity of the patient.
Portal "Eternal youth" http://vechnayamolodost.ru