Inflammasome–Caspase-1–Interleukin-1 beta pathway (Inflammasome–Caspase-1–IL-1β pathway)

The Inflammasome–Caspase-1–Interleukin-1 beta (IL-1β) pathway is a central signaling cascade in the innate immune system that regulates the maturation and secretion of potent pro-inflammatory cytokines [1, 5]. The process begins with the assembly of an inflammasome, a multi-protein complex typically consisting of a sensor (such as NLRP3), an adaptor (ASC), and the protease pro-caspase-1, in response to pathogen-associated or danger-associated molecular patterns (PAMPs or DAMPs) [2, 11]. Upon assembly, pro-caspase-1 undergoes auto-proteolysis to become active caspase-1, which then cleaves the inactive precursors pro-IL-1β and pro-IL-18 into their biologically active forms [1, 6]. Additionally, caspase-1 cleaves gasdermin D, leading to the formation of membrane pores and a specialized form of inflammatory cell death known as pyroptosis [5, 14]. Dysregulation of this pathway is a key driver in various chronic inflammatory and autoinflammatory conditions, including cryopyrin-associated periodic syndromes (CAPS), gout, atherosclerosis, and type 2 diabetes [1, 9, 12]. Therapeutic intervention strategies include the use of monoclonal antibodies to neutralize IL-1β, IL-1 receptor antagonists, and small-molecule inhibitors targeting NLRP3 or caspase-1 activity [3, 8].

Other names

NLRP3 inflammasome pathwayCaspase-1 signaling pathwayIL-1β maturation pathwayCanonical inflammasome pathwayInterleukin-1 beta converting enzyme pathway

Inhibition of NLRP3 inflammasome assembly, inhibition of caspase-1 enzymatic activity, or neutralization of interleukin-1 beta cytokine.