The NLRP3 inflammasome: a new player in neurological diseases

Abstract

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.

Exosomes Secreted From Bone Marrow Mesenchymal Stem Cells Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Pyroptosis in PC12 Cells by Promoting AMPK-Dependent Autophagic Flux

“…As a component of pyroptosis, NLRP3 inflammasome is of concern because it can be activated by various PAMPs and DAMPs and it is closely related to various human diseases (Gong et al, 2018 ; Liu et al, 2018 ; Eren and Özõren, 2019 ). When NLRP3 is assembled and activated, caspase-1 can be activated and turn pro-IL-1β and GSDMD into the bioactive cytokines IL-1β and GSDMD-N, respectively (Hou et al, 2018 ).…”

“…This effect was similar to the NLRP3 inhibitor MCC950 and was reversed by NLRP3 overexpression. Various studies have found that ROS represents a key signal that regulates the activation of the NLRP3 inflammasome (Tschopp and Schroder, 2010 ; Eren and Özõren, 2019 ). We found that the ROS level in the cells subjected to OGD/R was increased significantly and that BMSC-Exos could weaken this response, indicating that BMSC-Exos reduced pyroptosis mediated by the NLRP3 inflammasome.…”

Sinapine Thiocyanate Ameliorates Vascular Endothelial Dysfunction in Hypertension by Inhibiting Activation of the NLRP3 Inflammasome

“…The NOD-like receptor (NLR) is a pattern recognition receptor (PRR) family member, and these receptors are found in the cytosol and are able to identify pathogen-associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPS) ( Adachi and Tsuda, 2019 ). NLRP3 is the most studied member in the NLR family, and it is expressed in granulocytes, monocytes, dendritic cells, T cells, and epithelial cells ( Eren and Özören, 2019 ). The NLPR3 inflammasome consists of the NLRP3 receptor, the adaptor apoptosis-associated speck-like protein containing a CARD (ASC), and the effector cysteinyl aspartate specific proteinase (caspase-1).…”

Activation of alpha-4 beta-2 nicotinic receptor against cardiopulmonary bypass surgery induced brain injury by regulating NLRP3 pathway

“…Literature suggest that NLRP3 has a proven role in the neuronal dysfunction by enhancing the apoptosis through the activation of caspase pathway and NLRP3 inflammasome pathway reported to be involved in CPB surgery induced brain injury (Eren and Özören, 2019). ROS also contributes in the development of neuronal injury by regulating NLRP3 pathway (Abais et al, 2015).…”