The battle against the heart of Parkinson’s disease

Javier Alvarez Martin is not the kind of researcher who gives up. He has been battling Parkinson’s disease for many years. And this is what the Institute of Biomedicine and Molecular Genetics (IBGM) of Valladolid does. This professor of biochemistry and molecular biology It targets the underlying disease, which mainly causes movement disorders such as tremors, unsteadiness when walking, muscle stiffness or difficulty speaking. Because? It is the second most common neurodegenerative disease. Moreover, there is no definitive cure, only medications and treatments that control symptoms and improve patients’ quality of life.

His latest project is dedicated to a model of Parkinson’s disease they created in the C. elegans worm. “It’s a 1-millimeter-long worm that’s widely used to create disease models and in aging research,” he elaborates, before adding that to cause the pathology, it’s spiked with a chemical known to cause symptoms in a variety of people. species of animals.

In particular, he notes that in worms this reduces mobility and life expectancy, and also changes a number of parameters that can measure the synthesis of dopamine, a neurotransmitter involved in Parkinson’s disease.

. “We want to test a new target of action – the calcium cell signaling system. Calcium, in addition to being important for bones, has another key function in cellular functioning as an intracellular messenger and controller of processes such as muscle contraction, transmission of nerve impulses, or cellular energy production in mitochondria. It was by interfering with this calcium signaling system that we were able to largely reverse the changes in our Parkinson’s model,” he emphasizes.

In his opinion, this work is innovative because looking for new points of attack, new molecular targets, which help the scientific community access the source of the disease and cure it. “What we do is reduce the level of a protein that is responsible for flooding calcium into an intracellular compartment called the endoplasmic reticulum. This network is then responsible for releasing calcium so that it can perform its functions in response to various stimuli. To reduce levels of this protein we use RNA interference, which is a very specific mechanism, but there are also drugs being developed that can have a similar effect and are easier to administer. Then we have a whole series of worm measurements that allow us to see how the treatment reverses the changes in Parkinson’s pattern,” says Alvarez Martin.

For this IBGM researcher, The strength of this study is its action at the level of the molecular basis of this disease., as it is much better than treating symptoms only. “The problem is that the molecular basis of the disease is still unknown. From this point of view, our work is still at an early stage. “We have made significant improvements in changes in our model, but we still do not fully understand the molecular changes that cause Parkinson’s disease or the mechanisms involved in reversing symptoms,” he admits.

His group has been studying calcium-mediated signaling for many years. They recently began using the C. elegans worm model to study the involvement of calcium in aging. After this, he admits that it was a natural step to start using models of age-related neurodegenerative diseases such as Parkinson’s or Alzheimer’s disease and study the involvement of calcium in their development.

Another interesting point, he says, is that their proposed therapeutic targets have never before been proposed for neurodegenerative diseases. In this sense, it can boast of being a pioneering work that tries to get to the underlying mechanisms of the disease.

Looking to the future, calcium signaling systems are very complex and can be influenced at many levels, sometimes coordinated at multiple points. “We are currently reviewing all of these systems, looking for those that could also be useful as targets. “This will give us more tools against this disease and also allow us to better understand the mechanisms involved.”

When asked about the situation of research and innovation in Castile and León, the professor of biochemistry and molecular biology assures that there are many very talented researchers and groups, both in universities and in research institutes associated with the CSIC, that are promoting very interesting projects with very limited funding. In addition to this, he said, there are many researchers studying here who are currently working abroad and who could make a big contribution if they return, but they do not find space or adequate funding to do so.

In this regard, he regrets that it is very difficult for young people who are now writing their doctoral dissertation, or those who did so a few years ago and are now doing research outside Spain, to find places to return to. “It is very important that new blood comes into the universities and CSIC because there will be many retirees in the coming years and the renewal cannot be done immediately,” says Alvarez Martin.

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