Mitochondrial antiviral-signaling protein–NLR family pyrin domain containing 3–caspase-1 inflammasome axis (MAVS–NLRP3–Casp1 axis)

The Mitochondrial antiviral-signaling protein–NLR family pyrin domain containing 3–caspase-1 (MAVS–NLRP3–caspase-1) inflammasome axis is a critical signaling pathway that integrates mitochondrial stress with innate immune activation (Subramanian et al., 2013; Park et al., 2013). In this axis, MAVS serves as a mitochondrial scaffold that recruits the NLRP3 sensor protein, facilitating its oligomerization and the subsequent assembly of the inflammasome complex (Park et al., 2013). This assembly activates caspase-1, which proteolytically processes the pro-inflammatory cytokines IL-1β and IL-18 into their active forms and triggers pyroptosis via gasdermin D cleavage (He et al., 2016). The axis is particularly notable for its role in sensing sterile danger signals, such as cholesterol crystals or amyloid-beta plaques, which are central to the pathogenesis of chronic inflammatory diseases (NIH, 2025). Dysregulation of this axis is implicated in various conditions, including atherosclerosis, type 2 diabetes, and neurodegenerative disorders like Alzheimer's disease (Heneka et al., 2018; MDPI, 2026). Therapeutic strategies targeting this axis primarily focus on small-molecule inhibitors of NLRP3, such as MCC950 and DFV890, or biological agents that neutralize downstream cytokines (Coll et al., 2015; MacKay, 2025). While promising for treating chronic inflammation, targeting this pathway carries risks of immunosuppression and increased vulnerability to certain infections, as the inflammasome is essential for clearing specific pathogens (Mangan et al., 2018).

Other names

MAVS-NLRP3 signaling pathwayMitochondrial-associated NLRP3 inflammasomeRIG-I-MAVS-NLRP3 axisMAVS-NLRP3-Caspase-1 pathway

Inhibition of NLRP3 oligomerization and assembly, prevention of caspase-1 activation, and blockade of downstream pro-inflammatory cytokine maturation (IL-1β and IL-18).