Researchers Decipher Structure of Crucial Immune Molecule, Paving Way for Drug Design

Inflammasome is implicated in autoimmunity, heart disease, neurodegeneration, and more

Squares show the inflammasome from different angles. Some look like spoked wheels. Others look like sandwich cookies from the side.
Cryo-EM revealed the inflammasome from different angles. Images: Wu lab

 

Researchers in the lab of Harvard Medical School structural biologist Hao Wu have deciphered the step-by-step assembly of a molecular complex that’s crucial for fighting off infections but can also give rise to myriad diseases involving inflammation, from gout to Alzheimer’s to the cytokine storms of severe COVID-19.

The findings, published in Nature on Nov. 28, forge a path for researchers to develop drugs that regulate the complex’s formation and activity to treat or prevent the diseases it’s linked to.

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When viruses or bacteria enter the body, NLRP3 molecules inside white blood cells known as macrophages detect cell damage caused by the invaders and spring into action.

The molecules then somehow link with other proteins to form inflammasomes: disk-shaped structures that sound an alarm for the immune system to attack and tell infected or otherwise damaged cells to self-destruct.

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Video: Rick Groleau