Dual-use protein
The key protein of Alzheimer's disease can both help and harm
Glial cells (red) are more active in the mouse brain
with activated TREM2 protein (left).
(Washington University School in St.Louse).
American neurologists and immunologists from the University of Washington conducted a study that made it possible to clarify the true role of the TREM2 protein in the development of Alzheimer's disease.
Alzheimer's disease is one of the most common causes of dementia. Now there is no complete understanding among scientists of the causes of the development of this disease, therefore there are no effective means of its treatment. Recent studies have shown an important role in the development of the disease of one of the immune proteins of the brain – TREM2, mutations of the gene of which can significantly increase the risk of dementia.
The TREM2 protein is synthesized in microglial cells (immune cells of the brain) and is involved in a variety of processes related to inflammation, phagocytosis, proliferation and survival of nerve cells. It has been found that people with the TREM2 genetic mutation have a several-fold increased risk of developing Alzheimer's disease. Low synthesis of this protein leads to increased formation of toxic β-amyloid – one of the two main factors in the development of the disease. A new study by American scientists shows another, unexpected and opposite facet of the effects of the TREM2 protein.
The aim of the new work was to test the effect of the TREM2 protein on the second main toxic agent of Alzheimer's disease – tau protein. It is known that the formation of beta-amyloid in neurons at an early stage of Alzheimer's disease can last for several years without causing noticeable symptoms. The action of tau protein in the last stages of the disease, on the contrary, is very fast and immediately leads to disorders in the human brain.
Scientists took genetically modified mice with increased synthesis of tau protein. The mice were divided into two groups, one of which included rodents with the TREM2 gene turned off. When the experimental mice were examined at the age of 9 months, it turned out that animals with normal TREM2 had extensive accumulations of tau protein in the brain and damage to areas associated with memory. In rodents from the second group with a non-functioning TREM2 gene, the clinical picture, to the surprise of scientists, turned out to be much better. They had significantly less loss of neurons.
According to scientists, this difference is caused by the fact that microglia in mice with TREM2 was active, releasing compounds that damage and kill neighboring neurons. Microglia in mice without TREM2 was much less active, and their neurons were relatively protected.
Thus, scientists were able to find out the dual role of the TREM2 protein: in the early stages of the disease, it protects neurons from death, and in the later stages it helps to kill them.
"Reduced TREM2 function enhances the damage associated with β-amyloid. But as soon as the disease progresses, and a lot of tau protein accumulates in the brain, activated TREM2 microglia apparently begins to damage neurons," the authors write. According to them, these results should help in the development of an effective strategy to combat Alzheimer's disease.
The study is published in the journal Proceedings of the National Academy of Science of the USA.
Portal "Eternal youth" http://vechnayamolodost.ru