Researchers at the Institute of Biomedical Sciences at the University of São Paulo (USP) identified a substance, called AG-490, which prevented 60% of cell death in mice.
The findings, published in the journal Molecular Neurobiology, may point to new targets in the search for the treatment of Parkinson’s disease, characterized by the early death or degeneration of cells in the substantia nigra region of the brain, responsible for the production of dopamine (neurotransmitter).
The authors explain that the absence or decrease of dopamine affects the motor system, causing the characteristic symptoms of Parkinson’s, which include tremors, slowness of movement, muscle rigidity, imbalance, as well as changes in speech and writing. Patients may also experience non-motor symptoms, such as gastrointestinal, respiratory, and psychiatric changes. So far, there is no cure for the disease, only symptom control measures.
The research coordinated by Professor Luiz Roberto G. Britto was developed at the Cell Neurobiology Laboratory with the collaboration of specialists from the USP Institute of Chemistry and the University of Toronto, Canada.
“In mice, we were able to decrease about 60% of cell death by inhibiting TRPM2 – one of the calcium entry channels in brain cells. This was done with a substance based on the tyrphostine molecule, called AG-490,” says Britto in a statement. “Mice not given the substance performed 70% worse on behavioral tests,” he adds.
The expert explains that the strategy proved to be a possible intervention against one of the four ways known to science in which the disease causes the death of neurons.
“Among the causes are some metabolic dysfunctions and abnormal accumulation of proteins, neuroinflammation of the brain, oxidative stress caused by the accumulation of reactive oxygen species and an increase in the activity of calcium input channels – which we managed to prevent at least in part. ”, explains Britto.
According to the researcher, the overload of calcium in the body’s cells can lead to the activation of a series of enzymes, which degrade the structure of the cells, causing death.
“With the study, we came to the conclusion that when we blocked the channel, the degeneration of neurons, specifically in those regions where neurons are killed by the disease, greatly decreased. The same happened in the places where those neurons project and have synaptic contacts, which helped to preserve dopamine, a fundamental neurotransmitter for movements, among other functions”, he explains.
How the tests were performed
The tests were carried out on mice that were injected with the toxin 6-hydroxydopamine, which mimics the effects of Parkinson’s disease.
The animals were divided into two groups, only one of which received the substance AG-490. After six days, the researchers performed tests to assess the animals’ balance ability and other motor behaviors.
The analyzes also included counting neurons that produce dopamine in the substantia nigra, involved with the disease. The experts also studied brain regions associated with communication between neurons. The findings showed less damage with the administration of the substance, both in behavioral terms and in terms of the number of cells and affected sites.
next steps
The research results may point to ways in the search for a drug against Parkinson’s disease. For the advancement of research to the stage of clinical trials, which have the participation of human volunteers, further studies will be needed.
“In order for us to have a drug based on AG-490, we need to make sure that this substance works after the application of the toxin, since for now it has been administered at the same time as the injection of the toxin that produces the Parkinson’s model. In addition, it is necessary to study the possible collateral consequences of injecting the substance”, explained the USP professor who has been investigating the subject for more than ten years.
The research stage was developed during the doctoral thesis of the biologist Ana Flávia Fernandes Ferreira and had the support of the Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp).
Source: CNN Brasil
