Researchers have elucidated the structure of a central cellular inflammatory switch. Their work shows which site of the giant protein called NLRP3 inhibitors can bind to. This opens the way to develop new pharmaceuticals that could target inflammatory diseases such as gout, type 2 diabetes or even Alzheimer’s disease.
In their study, the researchers investigated a protein molecule with the cryptic abbreviation NLRP3. This is a kind of danger sensor in the cell: It sounds the alarm when the cell is under stress, such as from a bacterial infection or toxins.
NLRP3 then induces the formation of pores within the cellular membrane, which ultimately results in the cell’s death. Before that, however, the sensor molecule stimulates the formation of inflammatory messenger substances that are released through the perforated membrane. These so-called cytokines recruit more immune cells to the site and ensure that cells in the surrounding area commit suicide — thereby preventing a bacterium or virus from further spreading.
«The result is a massive inflammatory response,» explains study leader Prof. Dr. Matthias Geyer from the Institute of Structural Biology at the University of Bonn. «This is certainly very useful for the defense against pathogens. But if this response is overdosed or triggered by even harmless cues, it can lead to chronic inflammatory diseases — such as type II diabetes, gout, Crohn’s disease, or even dementias like Alzheimer’s.»
Targeted containment of inflammation
Researchers around the globe are therefore seeking for ways to target inflammatory processes without disrupting the entire mechanism of the immune response. As early as 20 years ago, the US pharmaceutical company Pfizer published an interesting finding in this regard: Certain active substances prevent the release of cytokines, the most important inflammatory messengers. How these CRIDs (Cytokine Release Inhibitory Drugs) do this, however, was unknown until now.
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Materials provided by University of Bonn. Note: Content may be edited for style and length.