Table 2 Inflammasomes Inflammasomes play a pivotal role in the pathogenesis of ALD.85 These intracellular multiprotein complexes are responsible for recognising danger signals, such as PAMPs and DAMPs, which trigger the activation, maturation and release of pro-inflammatory cytokines, including IL-1 and IL-18.126 127 Additionally, inflammasomes can initiate pyroptosis, a highly inflammatory form of programmed cell death that further contributes to liver damage.128 Among the various inflammasomes studied in ALD, the NLRP3 inflammasome is the most extensively investigated.129 The NLRP3 complex comprises the NLRP3 sensor, the adaptor protein apoptosis speck protein and pro-caspase-1.130 Activation of the NLRP3 inflammasome is a two-step process.131 First, PAMPs or DAMPs engage TLRs, leading to the activation of nuclear factor Kappa-light-chain-enhancer of activated B cells.131 This transcription factor induces the expression of NLRP3 and pro-inflammatory cytokines like pro-IL-1 and pro-IL-18.131 In the second step, NLRP3 oligomerises, forming a complex that activates caspase-1, which in turn cleaves pro-IL-1 and pro-IL-18 into their active forms
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if therapeutic goals are not achieved, PCSK9 inhibitors should be added
& Oikawa, S
