Intestinal infection and parkinsonism
In recent years, researchers have become increasingly interested in the connection between the immune system and Parkinson's disease. Using mouse models, they assessed the potential role of intestinal infection in this disease.
Parkinson's disease develops due to the slow depletion of dopamine–producing neurons in one of the parts of the brain - the substantia nigra. It plays an important role in movement, so clinically Parkinson's disease is manifested by tremor and muscle rigidity.
The main risk factor for developing Parkinson's disease is age, and as the population ages slowly, the number of cases is steadily increasing. Some experts believe that humanity is approaching a pandemic of Parkinson's disease; worldwide, between 1990 and 2015, the number of cases of Parkinson's disease doubled and exceeded 6 million. It is expected that by 2040 it will double again and reach 12 million.
Researchers have been studying Parkinson's disease for decades, but there are still questions about how and why brain cells are destroyed.
Parkinson's disease and the immune system
More recently, the link between the immune system and Parkinson's disease has come to the fore. Evidence is gradually accumulating that an autoimmune component plays an important role in pathogenesis.
About 10% of cases of Parkinson's disease are associated with mutations in genes that encode PINK1 and Parkin proteins involved in the excretion of damaged mitochondria. Carriers of these mutations are prone to developing Parkinson's disease at an earlier age – up to 50 years.
However, knockout of these genes in laboratory mice did not lead to the development of Parkinson's disease. This means that the loss of function of these proteins is not enough for the development of the disease. The researchers decided to identify other factors.
The picture has formed
The authors were looking for additional evidence that there is a link between PINK1 and Parkin proteins, mitochondria, the immune system and Parkinsonism. They suggested that mice with the PINK1 and Parkin genes knocked out did not develop Parkinson's disease due to the conditions of detention: the mice used in these studies usually do not come into contact with bacteria.
To test the hypothesis, the researchers infected young mice that lacked PINK1 and Parkin proteins with E. coli. This caused mild symptoms of intestinal infection.
As expected, contact with E. coli at a young age provoked the occurrence of Parkinsonian-like motor disorders in old age. The loss of dopaminergic neurons in the brain was confirmed. Treatment with levodopa improved the condition of mice – this proves that their disease is similar to human Parkinson's disease.
In mice with normal PINK1 and Parkin genes, the immune system properly handles pathogens. In animals with knocked–out genes, intestinal infection provokes an incorrect immune response - healthy cells are attacked.
Rich history
The results of this study are based on earlier work by the same group of researchers, which proved the connection between genes, mitochondria and the immune system.
They showed that the PINK1 and Parkin genes suppress the mitochondrial signaling pathway that triggers an immune response to infection.
In another study, scientists identified T-lymphocytes that respond to healthy tissues in the brains of mice. In a Petri dish, they attacked healthy neurons. The authors have created a pathophysiological model of the development of Parkinson's disease, in which an intestinal infection acts as a trigger. In the classical model of Parkinson's disease, dopaminergic neurons die due to the accumulation of toxic proteins inside cells.
A new study shows the role of an excessive immune reaction, which could have occurred even a few years before the disease, in the destruction of cells. It does not prove the autoimmune mechanism of all cases of Parkinson's disease, but suggests that the immune system plays a role.
The work was performed on mouse models, and there is no guarantee that the results will be confirmed in humans. In addition, not all people with Parkinson's disease carry mutations in the genes encoding the PINK1 and Parkin proteins, so it is not clear whether similar mechanisms are involved in all cases of the disease.
Article by D. Matheoud et al. Intestinal infection triggers Parkinson's disease-like symptoms in Pink1−/−mice published in the journal Nature.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to Medical News Today: How a gut infection might spark Parkinson's.