Targeting NLRP3 inflammasome for neurodegenerative disorders

Abstract

Neuroinflammation is a key pathological feature in neurological diseases, including Alzheimer's disease (AD). The nucleotide-binding domain leucine-rich repeat-containing proteins (NLRs) belong to the pattern recognition receptors (PRRs) family that sense stress signals, which play an important role in inflammation. As a member of NLRs, the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) is predominantly expressed in microglia, the principal innate immune cells in the central nervous system (CNS). Microglia release proinflammatory cytokines to cause pyroptosis through activating NLRP3 inflammasome. The active NLRP3 inflammasome is involved in a variety of neurodegenerative diseases (NDs). Recent studies also indicate the key role of neuronal NLRP3 in the pathogenesis of neurological disorders. In this article, we reviewed the mechanisms of NLRP3 expression and activation and discussed the role of active NLRP3 inflammasome in the pathogenesis of NDs, particularly focusing on AD. The studies suggest that targeting NLRP3 inflammasome could be a novel approach for the disease modification.