NLRP3 inflammasome
DENLRP3-Inflammasom
The NLRP3 inflammasome is a multi-protein alarm complex in your cells. It is built from three parts: a sensor (NLRP3), an adaptor (ASC), and pro-caspase-1. It assembles in response to many danger signals. Those include ATP, uric-acid crystals, cholesterol crystals, saturated fats, and mitochondrial ROS. Once assembled, it self-activates an enzyme, caspase-1. Caspase-1 then matures IL-1β and IL-18 for release. It also cuts gasdermin D to start pyroptosis. NLRP3 activity rises with age in many tissues. It feeds inflammaging, and is linked to atherosclerosis, type 2 diabetes, gout, and Alzheimer's. Trials are testing several drugs. There are selective NLRP3 blockers (like MCC950 analogues and inzomelid). There are downstream IL-1β antagonists (like canakinumab). And there is colchicine, which calms NLRP3-driven inflammation indirectly, by disrupting microtubules rather than blocking NLRP3 directly.
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Sources
- Latz E, Xiao TS, Stutz A. (2013). Activation and regulation of the inflammasomes. Nature Reviews Immunologydoi:10.1038/nri3452
- Tschopp J, Schroder K. (2010). NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production? Nature Reviews Immunologydoi:10.1038/nri2725
- Vandanmagsar B, Youm YH, Ravussin A, et al. (2011). The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature Medicinedoi:10.1038/nm.2279