An enzyme that plays an important role in regulating gene expression has been found to be vital for the dopaminergic neurons in the brains of adults. With these research results, University of Helsinki researchers believe they have found a new area for drug discovery to develop treatments for Parkinson’s disease, and new molecules are already under development.

A research group at the Institute of Biotechnology, led by Academy Research Fellow Andrii Domanskyi, set up a research model in which a molecule known as Dicer, one that regulates microRNA processing, was removed from the brains of mice.  

MicroRNA molecules are central to neuron function. As an individual ages, the amount of functional microRNAs in the cells diminishes. This leads to dysregulated protein production, increased cell stress and, ultimately, the death of the neuron.

In addition to ageing, the amount of microRNA is also diminished in cancer cells and in many neurological diseases such as Parkinson’s.

In the study, dopaminergic neurons of genetically modified mice began to degenerate and the mice developed symptoms associated with Parkinson’s disease soon after the removal of the Dicer enzyme. In another set of experiments, researchers found that stimulating the production of microRNA protected cells from stress and helped them survive.

 “We know that the dopaminergic neurons of the elderly have smaller amounts of Dicer and functional microRNA molecules. The new results indicate that a lower level of Dicer may accelerate the degeneration of neurons in Parkinson’s disease,” says Domanskyi.

The findings are significant and there are very few genes that are known to be crucial for survival of dopaminergic neurons. Cells use the information encoded in their DNA to direct the production of proteins which are crucial for the development and metabolism of the individual. This process is intricately controlled by various molecules, among them, microRNAs that regulate the amounts of proteins.

Domanskyi’s group is currently working on new molecules that would stimulate the production of microRNAs. Their efficacy in protecting dopaminergic neurons is currently being tested in animal models. The research may lead to new treatments for Parkinson’s disease.

There is currently no cure for Parkinson’s. However, many treatments which alleviate the symptoms have been developed in Finland. According to Domanskyi, it is impossible to conduct high-standard research in isolation.

 “High-quality research in our field requires both national and international cooperation. The good results at the University of Helsinki are due to the fact that in addition to a healthy infrastructure, we have many esteemed research groups working in close cooperation.”

Professor Mart Saarma from the Institute of Biotechnology says that Andrii Domanskyi has been one of the most successful recruitments during the past few years at the Institute. “Domanskyi spent several years in Germany working in Günther Schütz’s group and we were very happy that he chose to come to Finland to continue his research,” states Professor Saarma.

Researcher contact details:

Andrii Domanskyi

Original study:

Chmielarz P, Konovalova J, Najam SS, Alter H, Piepponen TP, Erfle H, Sonntag K, Schütz G, Vinnikov IA, Domanskyi A, Dicer and microRNAs protect adult dopamine neurons. Cell Death Dis, 8(5): e2813, 2017

http://www.nature.com/cddis/journal/v8/n5/full/cddis2017214a.html