Transposons and tau protein
The accumulation of tau protein in brain tissue is one of the key characteristics of Alzheimer's disease. It leads to progressive death of nerve cells. For many years, scientists have been trying to understand why a cell dies when tau protein aggregates in it. The only thing that was found out was that such neurons lose genomic stability.
Genome instability refers to an increased propensity for changes in genetic material – mutations or other disorders. Researchers from Baylor College of Medicine (USA), led by Joshua Shulman, focused on finding a causal relationship between the accumulation of tau protein in neurons and genomic instability.
Previous studies of the brain tissue of patients with various neurological diseases and animal models have shown that not only genomic instability develops in neurons, but also transposons are activated – short fragments of DNA that do not participate in protein synthesis, but behave more like viruses: they create their own copies, which are inserted into the genome and lead to mutations. Most of the transposons are in an inactive state in the cell, but they can "wake up" during the aging process of the body or in certain diseases. The authors set out to test the degree of activity of these DNA fragments in the accumulation of tau protein associated with Alzheimer's disease.
The researchers analyzed data from a large population-based study conducted at Rush University Medical Center in Chicago. In this study, participants were monitored during life, and after death, the state of the brain was assessed.
Shulman and co-authors studied 600 brain samples of people with a high content of tau protein in neurons. They then estimated the number of active transposable genetic elements. To do this, it was necessary to develop special software. A statistical analysis was carried out in which the number of active transposable elements was compared with the accumulation of tau protein. The researchers found a significant relationship between these indicators.
Another study by the authors showed that tau protein disrupts the tightly packed architecture of the genome. It is believed that it restricts the work of genes, and a violation of packaging can activate them. The storage of tightly packed DNA may be an important mechanism for suppressing the activity of transposable elements that lead to mutations.
Thus, tau protein probably affects the architecture of the genome, and this is one of the mechanisms of activation of transposable genetic elements, accumulation of mutations and death of neurons in Alzheimer's disease.
To confirm these results, experiments were conducted on fruit flies with a model of Alzheimer's disease. The changes that tau protein triggers were similar to those observed in postmortem human brain samples: transposable elements were activated, eventually leading to neurodegeneration.
The authors believe that the data obtained in their work carry new and potentially important ideas that will help to fully uncover the mechanisms of Alzheimer's disease, but there is still a lot of work in this direction.
Article C. Guo et al. Tau Activates Transposable Elements in Alzheimer's Disease published in the journal Cell Reports.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Baylor College of Medicine: Research links Tau aggregates, cell death in Alzheimer's.