AG-490, based on the molecule tyrphostin, was tested on mice and prevented 60% cell death.
Researchers at the University of São Paulo (USP) have identified a substance that can stop the progression of Parkinson’s disease. AG-490, based on the tyrphostin molecule, was tested in mice and prevented 60% cell death. It inhibits one of the channels for calcium to enter the brain cells, one of the mechanisms by which the disease causes the death of neurons. There is no cure for Parkinson’s, only control of symptoms.
“We suggest that it is this compound that could one day, after much research, that we continue, be used in human medicine,” said Professor Luiz Roberto Britto, who is coordinating the project with researchers at the Institute of Chemistry. in. USP and University of Toronto, Canada. The results were published in the journal Molecular Neurobiology.
Parkinson’s disease is characterized by early death or cell corruption in the region responsible for the production of dopamine, a neurotransmitter. The absence or decrease of dopamine affects the motor system, causing tremors, slowing of movement, muscle stiffness, imbalance, as well as changes in speech and writing. The disease can also cause gastrointestinal, respiratory and psychiatric disorders.
“The disease is progressive, neurons continue to die, this is the big problem. At first 10% die, then 20%, a little more, in fact the diagnosis is practically only made when more than 60% die in regions specific to the brain, ”explains Britto. Identification of this substance may stabilize the disease to a certain extent. “It would no longer be a cure, but it would at least keep it from getting older and more complicated. The person died later from complications. “
Substance
Britto explains that AG-490 is a synthetic substance already known in biochemistry. The inspiration for the work came from a model applied in Canada, which showed that the substance had a protective effect on stroke, also in animal science. He adds that the cause of the disease is not known for sure, but some favor the death of neurons. “Accumulation of free radicals, inflammation of the nervous system, errors in some proteins and excess entry of calcium into the cells,” he cites.
That’s why the study began investigating this calcium entry channel called TRPM2. It can be concluded, with the research, that when the duct is blocked, the corruption of neurons, especially in the regions where they are killed by the disease, greatly decreases. “The idea is that, perhaps, if we block these channels with the substance, or others that appear, we may be able to, at the very least, prevent the progression of the disease after it sets in,” says the researcher.
The analysis continues and now one of the first steps is to find out how the substance behaves with a subsequent application of toxins that cause the disease. Britto explains that in the model used, the toxin and the compound were applied almost simultaneously. Researchers also want to know if the compound is administered days after the toxin will lead to the protection of neurons.
“Another thing we need to do, and we already have the animals for that, is to use a genetically modified mouse model, which does not have this TRTM2 channel. We hope that animals that do not genetically contain these calcium channels are theoretically more resistant to this pattern of Parkinson’s disease, “he added.
It will also be necessary to assess possible side effects. “These calcium channels are in many places in the nervous system and outside the nervous system as well. Blocking the channels can have consequences elsewhere. We need to evaluate that.” The analysis continues with the support of the Fundação de Amparo à Pesquisa do Estado de São Paulo and the National Council for Scientific and Technological Development (CNPq).
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