Therapeutic potential of the target on NLRP3 inflammasome in multiple sclerosis

Inflammasomes are multi-protein macromolecular complexes that typically comprise of three units, a sensor, an adaptor and procaspase-1. The assembly of each inflammasome is dictated by a unique pattern recognition receptors (PRRs) in response to pathogen-associated molecular patterns (PAMPs) or other endogenous danger associated molecular patterns (DAMPs) in the cytosol of the host cells, and promote the maturation and secretion of IL-1 beta and IL-18 during the inflammatory process. Specific inflammasomes are involved in the host defense response against different pathogens, and the latter have evolved multiple corresponding mechanisms to inhibit inflammasome activation. The nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome is the best understood in terms of molecular mechanisms, and is a promising therapeutic target in immune-related disorders. Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination of white matter in the central nervous system, increased levels of IL-1 beta in the cerebrospinal fluid (CSF) of relapsed patients, and deposition of caspase-1 in the spinal cord. The direct involvement of the NLRP3 inflammasome in the occurrence and development of MS was ascertained in the experimental autoimmune encephalomyelitis (EAE) animal model. In this review, we have focused on the mechanisms underlying activation of the NLRP3 inflammasome in MS or EAE, as well as inhibitors that specifically target the complex and alleviate disease progression, in order to unearth new therapeutic strategies against MS. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

Inflammasomes are multi-protein complexes that regulate the maturation and secretion of IL-1 beta and IL-18 in response to PAMPs or DAMPs in host cells. The NLRP3 inflammasome is well-understood in molecular mechanisms, serving as a promising therapeutic target in immune-related disorders such as multiple sclerosis (MS). Investigation of NLRP3 activation mechanisms in MS and experimental models may lead to new therapeutic strategies for the disease.