Suraj Rajan / Wikimedia Commons
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American scientists have found a mechanism that allows young mice to defeat Parkinson’s disease at an early stage. This is the enzyme glucocerebrosidase, with the help of which immune cells break down extracellular accumulations of proteins. Young mice have a lot of it, so even “infection” with Parkinson’s disease goes away in a few months. And in old mice it is not enough, so they have protein lumps settle in the brain. Adding this enzyme to the body can help cope with Parkinson’s disease – not only in mice, but probably in humans. The work was published in the journal. Nature neuroscience.
One of the main signs of Parkinson’s disease is the accumulation of lumps of alpha synuclein protein in the nervous tissue of the brain. When they are found in sufficient quantities there, it is no longer possible to stop the disease. But some time ago, scientists noticed that long before a person was diagnosed, the first symptoms of the disease appear in the intestines. It is believed that from there accumulations of alpha synuclein can enter the vagus nerve and reach the brain through it – in mice it takes about a month.
A team of researchers led by Viviana Gradinaru from the University of California, Technological University, decided to look in detail at what exactly happens in the intestine affected by alpha synuclein. To do this, they worked with healthy adult mice. Since these animals themselves do not suffer from Parkinson’s disease in order to create similar symptoms in them, scientists introduced them to the precursors of the protein lump – threads that other alpha-synuclein molecules can then stick to – directly into the muscularis of the duodenum, where many processes of the vagus are located a nerve.
3 months after the injection, the scientists noticed signs of intestinal dysfunction in the experimental group of animals: the weight of excrement decreased by a quarter, and the time for food to move through the digestive tract, on the contrary, increased one and a half times.
Then the researchers studied in more detail the pathological process in the intestinal wall. They found that within a week after the injection, inflammation develops in the affected tissue – at least, the concentration of the pro-inflammatory protein IL-6 increases. But clusters of alpha-synuclein aggregates began to appear later. By the 60th day they reached a peak, but by the 120th they not only did not become more, but even less, however, insignificantly. Therefore, the authors of the work suggested that in the intestines of animals some way of eliminating protein lumps was launched.
Researchers noticed the same effect in the development of other signs of the disease. In mice that were injected with alpha-synuclein, coordination problems started on day 60 (for example, when they had to go down the perch into their cage), but by day 120 they disappeared.
Since age is considered one of the main risk factors for the development of Parkinson’s disease, scientists have suggested that the results of the experiment turn out to be different for older mice. Indeed, more alpha synuclein was formed in their intestinal wall than in young animals. Both digestion and motor skills continued to deteriorate 120 days after the injection. In addition, the concentration of dopamine (a neurotransmitter that is deficient in Parkinson’s disease) in the striatum of the brain in elderly animals fell three times in 4 months compared with young mice.
Researchers attribute different results for young and old mice to the activity of macrophages – immune cells that perform the work of scavengers in the tissue, destroying the accumulation of proteins between cells. They do this using organelles of lysosomes and, in particular, the enzyme glucocerebrosidase. In the intestines of older animals, scientists found half as much of this enzyme as in young ones. Apparently, it is simply not enough to cope with lumps of alpha synuclein in time.
Researchers then suggested that the addition of glucocerebrosidase might be enough to prevent the development of Parkinson’s disease. As a model, they took genetically modified mice, in the cells of which alpha synuclein is constantly produced, and then accumulates in the intestine even more than in old animals after injection. Scientists modified mice introduced them a viral vector with the glucocerebrosidase gene and found that they have partially, though not completely, restored intestinal functions.
The authors of the work do not exclude the possibility that gene therapy – the introduction of the glucocerebrosidase gene – may be a good way to treat Parkinson’s disease in the early stages. And since it is much easier to deliver the gene to the intestine than to the brain, this option may turn out to be more realistic than other methods of therapy related directly to the nervous tissue of the brain.
Previously, scientists suspected oral bacteria of causing Alzheimer’s disease. And with the transfer of human amyloid beta, it was possible to infect laboratory mice with this disease (for more information on whether this threatens people, read our blog “Dementia is contagious?”). In addition, in some experiments, even diabetes was contagious.
Polina Loseva
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