Nlrp3-flox Mouse

Nlrp3, also known as NACHT, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3, is a key component of the NLRP3 inflammasome. The NLRP3 inflammasome is a multi-protein signaling complex that triggers the activation of inflammatory caspases and the maturation of interleukin-1β. It is involved in the body's inflammatory response to various "danger" situations such as infection and metabolic dysregulation, and has been linked to numerous autoinflammatory and autoimmune diseases [2].

Mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, which in turn activates the NLRP3 inflammasome. Inhibition of the voltage-dependent anion channel, which dysregulates mitochondrial activity, suppresses both ROS generation and inflammasome activation, indicating that NLRP3 inflammasome senses mitochondrial dysfunction [1]. Different NLRP3 stimuli cause the disassembly of the trans-Golgi network (TGN). NLRP3 is recruited to the dispersed TGN through an ionic bond with phosphatidylinositol-4-phosphate (PtdIns4P), leading to its aggregation and activation [3]. Palmitoylation of NLRP3 Cys126 by ZDHHC7 promotes NLRP3-mediated inflammasome activation, and perturbation of this palmitoylation diminishes NLRP3 activation in macrophages and in vivo [4].

In conclusion, NLRP3 plays a crucial role in the inflammatory response by sensing mitochondrial and organelle dysfunction. Its activation is regulated by multiple mechanisms related to organelles and post-translational modifications. Understanding NLRP3 function through model-based research, especially in relation to its role in various diseases such as cancer, liver injury, cardiovascular diseases, and COVID-19, may offer potential therapeutic strategies for these conditions [5,6,7,8].