A Franco-Belgian study shows that a single protein is at the origin of Parkinson’s disease and another rare degenerative pathology. A major advance in the understanding of these two diseases.
The same protein toxic to the brain, but two diseases. A Franco-Belgian team has just demonstrated that Parkinson’s disease and multi-system atrophy (MSA), two neurodegenerative diseases, have the same biological cause. Only one characteristic separates them, explain the researchers in the journal Nature : the form in which the alpha-synuclein protein aggregates.
Two forms, two diseases
Alpha-synuclein is a protein whose function is still poorly identified, but necessary for neurons to communicate with each other. When its form is functional, it does not present a danger to the brain. But there are so-called non-functional forms which can be toxic and which have the capacity to aggregate infinitely. “It is an irreversible reaction which ends up recruiting all the similar proteins of the cell, explains to Why actor Ronald Melki, research director at CNRS and co-author of the study. This disrupts the membrane of the neuron, which is very important because it allows nerve impulses to pass. “
The team from the Institute of Neurosciences in Saclay (Essonne), led by Ronald Meki, isolated different types of alpha-synuclein aggregates. The researchers therefore assumed that, depending on the assemblage, the disease induced was not the same.
To illustrate the discovery, the research director uses pasta, “no doubt because I’m greedy,” he jokes. Some aggregates therefore look like linguine, long and wide pasta, others like spaghetti, cylindrical and full.
“So we prepared these aggregates, and we injected them into the brains of rats,” says Ronald Melki. These rodents developed different diseases, depending on the type of aggregates injected into them. This allows us to better understand the genesis of the disease.
All you need to know about Parkinson’s disease
How is the shape of the aggregates defined?
“In a test tube, small variations in the conditions of aggregation will define the shape of these clusters”, summarizes Ronald Melki. Depending on the salt concentration, the temperature, this will change. “These parameters are not totally artificial,” emphasizes this researcher. The neuron in the intestine does not have the same temperature as a neuron in the brain. The cell also has compartments, some of which are acidic, he adds. The lysosome, for example, is a place where proteins break down that are no longer functional. It has a slightly acidic pH. “
A diagnosis by blood test
After successfully injecting the aggregates into the brains of the rats, the researchers attempted another mode of administration: through blood. “The objective is not to show that these diseases are infectious, but to show that the aggregates pass from one cell to another”, underlines Ronald Melki. Researchers have shown that when injected into the blood, abnormal proteins reach the brain.
An observation that contradicts the idea that the brain is isolated from the rest of the circulatory system. “But you have to read it the other way around,” warns the research director. The aggregates that form in the brain can diffuse into the blood. “It would therefore be possible, if we are to believe these results, to detect Parkinson’s disease even before the onset of symptoms, through a blood test. “It’s doable, we now have to create the tool for, but we will need a little time,” recognizes Ronald Melki.
But this researcher is full of hope. These results made him imagine a new method of treatment: attracting aggregates out of the brain, trapping them there in order to interrupt the progression of the disease. He does not hesitate to compare his work with that carried out a century ago in bacteriology: “At the time, we did not understand how bacteria worked. Today, we understand it and we create antibiotics. This understanding will lead to drug proposals, ”he postulates.
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