There are some things we are better off without. Our lungs would be happier if never exposed to cigarette smoke. Our livers would be healthier if never stuffed with fat. Our arteries would be content without being clogged with cholesterol. And, some scientists argue, our brains would stay sharper without the amyloid-β plaques and tau tangles that accumulate in old age. All these things have one thing in common: they incite inflammation in our bodies. And they do so by activating a hypersensitive protein called NLRP3.
A protein called NLRP3 has been linked to a suspiciously long list of conditions, including atherosclerosis, Alzheimer’s disease, inflammatory bowel disease, and nonalcoholic steatohepatitis. It’s part of a large protein complex called the inflammasome that, when activated, triggers a chain of events that causes cells to erupt and spill an inflammation-inducing soup. Biotech start-ups and pharma companies are now eagerly developing NLRP3 inhibitors that they think could address a wide swath of common diseases. But drug hunters face a daunting task: many features of the inflammasome, including its exact structure, remain a mystery.
For that reason, Kate Schroder sometimes wonders if we’d be better off without NLRP3.
Schroder, one of the world’s leading experts in inflammasome biology, has studied NLRP3 for over a decade, and today she directs a center at the University of Queensland dedicated to inflammasomes. NLRP3 is the most deeply researched, probably the most poorly understood, and undoubtedly the most perplexing member in a family of protein complexes called inflammasomes. These complexes are found in our immune cells, where they instigate inflammation—lots of it. The NLRP3 inflammasome in particular is a culprit in a suspiciously long list of diseases.