The NLRP3 inflammasome: a new player in neurological diseases

Abstract

Inflammasomes are supramolecular protein complexes implicated in the detection of pathogens or danger-associatedmolecules and are responsible for mounting the first line of innate immune response to counteract these signals and restore tissuehomeostasis. Among different inflammasomes identified so far, NLRP3 is of main interest since mutations in Nlrp3 gene are associatedwith autoinflammatory diseases such as Muckle–Wells syndrome, neonatal onset multisystem inflammatory disease, and familial coldurticaria/autoinflammatory syndrome. On the other hand, whereas other inflammasomes are mainly detectors of specific molecularmotifs, NLRP3 is acting as a general sensor of cellular perturbations including potassium efflux, lysosomal damage, and ROS production.Besides this central role of NLRP3 in inflammation, recent publications show that the NLRP3 inflammasome is also involved in thephysiopathology of several neurological disorders including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. This reviewgives an overview of the established functions of the NLRP3 inflammasome in mediating inflammation in macrophages and describesits recently discovered roles in neurological disorders in promoting neuroinflammation, as well as modulating key proteins mediatingthe disorders. Finally, we discuss the targeting of NLRP3 in neurological diseases and present some examples of NLRP3 inhibitors thatcould be used in neurological disorder treatments.