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.