Fig. 6

Drugs targeting inflammasome signaling in MS and EAE. Interferon (IFN) regulates the transcriptional level of signal transducer and activator transcription 1 (STAT1) to suppress activity of the (NLR) family pyrin domain-containing 1 (NLRP1) and NLRP3 inflammasomes. STAT1 target gene products directly repress these inflammasomes. Additionally, IFN/STAT1 pathway increases IL-10 synthesis in macrophages, IL-10-mediated STAT3 activation, and the suppression of interleukin (IL)-1β precursor synthesis by activated STAT3. Ketotifen is an anti-histamine that inhibits mast cell degranulation to block activation of the NLRP3 inflammasome. MCC950 directly targets the NLRP3 NACHT domain and interferes with the Walker B motif function, preventing NLRP3 conformational change and oligomerization. IC100, a humanized monoclonal antibody, binds to apoptosis speck-like staining protein containing a CARD (ASC) and prevents recruitment of ASC into the NLRP3 signaling complex and blocks formation of ASC specks intracellular and extracellularly