The NLRP3 inflammasome: a new player in neurological diseases

摘要

Inflammasomes are supramolecular protein complexes implicated in the detection of pathogens or danger-associated molecules and are responsible for mounting the first line of innate immune response to counteract these signals and restore tissue homeostasis. Among different inflammasomes identified so far, NLRP3 is of main interest since mutations in Nlrp3 gene are associated with autoinflammatory diseases such as Muckle-Wells syndrome, neonatal onset multisystem inflammatory disease, and familial cold urticaria/autoinflammatory syndrome. On the other hand, whereas other inflammasomes are mainly detectors of specific molecular motifs, 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 the physiopathology of several neurological disorders including Alzheimer?s disease, Parkinson?s disease, and multiple sclerosis. This review gives an overview of the established functions of the NLRP3 inflammasome in mediating inflammation in macrophages and describes its recently discovered roles in neurological disorders in promoting neuroinflammation, as well as modulating key proteins mediating the disorders. Finally, we discuss the targeting of NLRP3 in neurological diseases and present some examples of NLRP3 inhibitors that could be used in neurological disorder treatments.