A research group has studied the activity of a gene associated with Parkinson’s disease, paving the way for the development of new therapeutic strategies both for Parkinson’s disease and cancer.

This study, which was conducted by researchers from the Institute of Molecular Medicine (IMM), led by Tiago Outeiro, and by other researchers in Germany and in the United Kingdom, has revealed that Parkinson’s may have a genetic cause – evidence has pointed to environmental causes until recently – thus bringing new hope for its treatment.

“We have tried to study one of the genes associated with Parkinson’s disease, namely that which encodes the DJ-1 protein. This gene is also associated with cancer because the protein function is believed to be related to oxidative stress response,” said Tiago Outeiro to Lusa, the Portuguese News Agency.

This means that once the function of the defective gene is identified, it will hopefully be easier to find out “where things went wrong.” The DJ-1 protein is a particularly interesting example as this gene is what triggers various forms of Parkinson’s but is also linked to cancer, Alzheimer’s and other neurodegenerative disorders, which suggests that it plays an important role in the protection against ageing effects.
As the study of human proteins “is complex”, simpler models have been used to study the function of this protein and discover what causes such diseases.

“With that in mind, we used yeast, an organism with cells like those of other organisms, humans included. We drew on the similarity between yeast and human cells and studied the gene [DJ-1], in yeast, which has four proteins – HSP 31, HSP 32, HSP 33, and HSP 34. We studied what they do in the cell and how they respond,” he said.

The research team realised that, in yeasts, DJ-1 deletion from the genome affects various mechanisms of cell protection and ultimately yeast survival.

Outeiro believes that the “innovation” of this research lies in the fact that “these proteins are involved in the regulation of a TORC pathway, which is highly important as it regulates many cellular functions including autophagy – protein degradation for recycling in cells.”

It was thus possible to understand where the DJ-1 of yeast acts: it modulates the TORC protein that regulates the ageing process, achieving a balance between protein formation and destruction, which points to the fact that this molecule may be the key to Parkinson’s disease.

“While regulating this TORC pathway, [HSP proteins] regulate many processes within the cells. If we understand this we will be able to understand where to act so as to prevent or promote processes within cells,” Outeiro added.

The novelty of this research is “the use of yeast to study the process of Parkinson’s disease, the function of these proteins and of the DJ-1 gene,” he said.

In Outeiro’s view, this discovery opens up new doors: “if we find out how these proteins act we will be able to develop therapeutic strategies to manage the disease.”

A pioneer study recently undertaken in Portugal by the Portuguese Movement Disorder Society has revealed that there are nearly 13,000 people suffering from Parkinson’s disease, the second most prevalent neurodegenerative disease.

It is estimated that there are around 12 million people worldwide suffering from Parkinson’s disease, “and this number is likely to increase as the world’s population is ageing,” Outeiro added.

This study will be published in the scientific journal PNAS.

Source: Lusa/The Sol newspaper