The little protein engine that could

Of all the elements that make up the inflammatory response, none is more intriguing than the inflammasome – a machine-like protein complex at the heart of inflammation and disease.

Inflammasomes are part of the innate immune system and operate at a molecular level. They are triggered when an infection is detected and then activate specific cytokines – messenger proteins that tell immune cells that they should respond to the threat.

But inflammasomes can also be triggered by non-microbial molecules that might indicate an injury. Genetic mutations in inflammasome components can be inherited and also cause inflammatory disorders.

When everything is working as it should, the threat is resolved, and the inflammasome’s in-built timer switch ensures that the inflammasome only operates for a specific length of time.

As the head of IMB’s Centre for Inflammation and Disease Research, Professor Kate Schroder, explains, “if the inflammasome continues to fire, inflammation can become chronic, with disastrous results”. 

Inflammasome-linked cytokines have been identified as the drivers of the inflammatory component of numerous chronic diseases including gout, diabetes, Alzheimer’s disease and fatty liver disease.

“If the disturbance can’t be cleared, such as in the case of amyloid plaques in Alzheimer’s disease, these molecular machines continue to fire, resulting in neurodegenerative damage from continuous inflammation.”

Inflammation and Alzheimer’s

Professor Schroder is studying how the inflammasome works during infection and how it can misfire in human inflammatory disease. By understanding how unhealthy inflammation begins, she hopes to design new strategies to treat many common diseases.

One experimental strategy used in Professor Schroder’s lab is to use gene-editing technologies to alter the inflammasome’s in-built timer – in effect, turning up or down the volume on unhealthy inflammation – to understand its impact on disease.

Another clinical strategy is the development of drugs that could inhibit the inflammation response, which are currently being commercialised by drug development company, Inflazome Ltd.

The Edge - Inflammation