Pharmacological targets at the lysosomal autophagy-NLRP3 inflammasome crossroads.

Many aspects of cell homeostasis and integrity are maintained by the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome. The NLRP3 oligomeric protein complex assembles in response to exogenous and endogenous danger signals. This inflammasome has also been implicated in the pathogenesis of a range of disease conditions, particularly chronic inflammatory diseases. Given that NLRP3 modulates autophagy, which is also a key regulator of inflammasome activity, excessive inflammation may be controlled by targeting this intersecting pathway. However, specific niche areas of NLRP3-autophagy interactions and their reciprocal regulatory mechanisms remain underexplored. Consequently, we lack treatment methods specifically targeting this pivotal axis. Here, we discuss the potential of such strategies in the context of autoimmune and metabolic diseases and propose some research avenues.

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Déclaration de conflit d'intérêts

Declaration of interests S.M. is named as a co-inventor on CNRS-ImmuPharma patents relating to the P140 peptide. She declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The other authors declare no competing interests.