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MicroRNA: so small but so very important

The discovery in 2001 of the importance of microRNAs turned the world of molecular biology upside down. The small particles of RNA also attracted the attention of university lecturer Erno Vreugdenhil. Vreugdenhil: ‘Within five to ten years the first microRNA-directed medicines will come onto the market.’

Interesting drug target

The glucocorticoid receptor (red) and microRNA-124 (green) are present in the same nerve cells of the hippocampus, an area of the brain that is involved in learning and memory formation.

For many years, RNA was thought to be no more than a messenger: a copy of the DNA that ensures that DNA can be translated into proteins. 'Now it seems that a large part of the RNA doesn't code at all for a protein,' explains Vreugdenhil. ‘MicroRNAs are very small pieces of RNA, which have a strong position in the cell. They can bind to RNA that codes for a protein, to repress this protein. MicroRNAs are involved in a variety of disease processes, playing a role in different types of cancer, for instance. Breast cancer is often caused by an error in the production of RNA. This regulatory role makes microRNA very interesting as a drug target.' 

Stress and the brain

Vreugdenhil himself studies the effect of stress on the brain. 'Stress causes the release of stress hormones, the so-called glucocorticoids. These hormones have an effect on cells where glucocorticoid receptors are present. These include many different types of cells, including brain cells.  Medicines such as prednison and dexamethason work via this receptor. The effectiveness of the medicines depends on the amount of a receptor on a cell, and specific microRNAs seem to regulate the expression of this receptor.'

Clinically interesting

Vreugdenhil has discovered that there is a microRNA specifically for the brain, and that this microRNA regulates the amount of the glucocorticoid receptor. He published an article on the subject in the journal  Endocrinology in January 2009 Clinically, the discovery is very interesting. 'Chronic use of medicines such as prednison can have side-effects, including depression. Chronic stress, where stress hormones are continuously being produced, is a further important factor in depression. MicroRNAs specifically for brain cells offer the possibility of regulating the glucocorticoid receptor in the brain. The receptor in other cells, such as those in the immune system, is unaffected. Once you are able to regulate the influence of stress on the brain by developing a specific microRNA therapy, you have acquired a very effective tool.' 

‘Omdat onderzoekers nergens ter wereld microRNA functioneel konden duiden, werd gedacht dat deze kleine stukjes RNA niet meer waren dan afbraakproducten.’ 

We simply ignored it

If microRNA plays such a crucial role in the human body, how is it that it was not discovered until 2001?  Vreugdenhil explains: 'From the point where researchers started working on RNA, it became apparent that there were very many very small pieces of RNA.  As it was impossible for researchers anywhere in the world to explain the function of microRNA, it was assumed that these small particles of RNA were nothing more than waste products. They were simply thrown away. It was only in 2001, when it became apparent that people had far fewer genes than expected, that people started to look for different forms of protein regulation.  And then microRNA was discovered.  In fact, we have had microRNA in front of our noses for thirty years, but it was dismissed as a waste product.  We simply ignored it.'

All about biology

Through his research into stress and the glucocorticoid-receptor, Vreugdenhil soon came across microRNA. Following the discovery of the pieces of RNA, he was also one of the first in the Netherlands to carry out research on it. In January he received an award from the Leiden Amsterdam Center for Drug Research, primarily because he is continually introducing innovative research.  But he doesn't do it for the fame: ' I certainly find it satisfying, but it is for me all about biology. I want to introduce new techniques to learn new things.' 

Made up for lost time

Since the discovery of the function of microRNA, biology has made up for lost time. 'Developments are coming thick and fast. Clinical trials are already being conducted with molecules which can influence the activity of microRNA. I, too, am involved in setting up a programme in which microRNA is viewed as a drug target.  With different types of illnesses, errors in the production of microRNA play an important role, and these errors have to be corrected. It will not be long before there are medicines on the market directed at microRNA.'

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