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Danish researchers map key disease mechanism – and describe a completely new protein

It is vital for the immune system to kick into gear when the body is under attack, for instance by a pathogenic virus. However, problems can arise if the immune system is overstimulated.
25 researchers from Aarhus University (AU) have examined this very scenario in a scientific report, recently published together with colleagues from Norway, the USA, France and Japan in the prestigious scientific journal Nature Immunology.

The project, which is funded by the Lundbeck Foundation, the Danish Council for Independent Research and the EU, among others, involves considerable detective work by the researchers, who have combed through large volumes of evidence in the hope of unveiling a real villain. And according to Professor Søren Riis Paludan from AU, who headed the project, it worked:

‘We now have an understanding of a biochemical signalling pathway which, in humans, is certainly involved in a number of diseases when it is overactivated. One of these diseases is lupus, a chronic inflammation of the connective tissue.’

However, overactivation of STING, as the signalling pathway is called, may well be the cause of a good deal more misery. Professor Paludan explains:

‘Numerous animal trials indicate that STING could also be involved in the formation of blood clots as well as development of some of the neurodegenerative diseases, primarily Parkinson’s.’
It remains unclear whether this is the case when people develop these diseases – but this is something the 25 Aarhus researchers will now investigate more closely.

A signal to clear up
But what does STING actually do? To make a long story short, STING’s job as a biochemical signalling pathway is to activate the immune system. Professor Paludan clarifies:

‘If, for some reason or other, some of our cells go astray, STING will make sure that a signal is sent to the immune system to begin immediate clear-up. And the same applies if foreign DNA enters our body, for instance in the form of an infection.’

Professor Paludan explains that the signal is given via a protein, which has been labelled STEEP, and his research group discovered and described this protein:

‘When we were trying to identify how STING actually works, we began by using a variety of investigative techniques to search for previously unknown proteins that interact with this biochemical signalling pathway. And that’s how we found STEEP, the new protein.’

The protein is found in humans and other mammals. However, Professor Paludan explains that it is actually a very well-preserved protein and it has been involved in the evolutionary process for so long that it also occurs in insects.

Professor Paludan believes that in addition to giving us a better understanding of pathogenic processes, for instance in the case of lupus, this new knowledge about STING and STEEP will, in time, be useful when designing novel drugs.

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