| First Author | Xie S | Year | 2017 |
| Journal | FEBS Lett | Volume | 591 |
| Issue | 18 | Pages | 2836-2847 |
| PubMed ID | 28787755 | Mgi Jnum | J:244322 |
| Mgi Id | MGI:5913101 | Doi | 10.1002/1873-3468.12782 |
| Citation | Xie S, et al. (2017) A rapid administration of GW4064 inhibits the NLRP3 inflammasome activation independent of farnesoid X receptor agonism. FEBS Lett 591(18):2836-2847 |
| abstractText | GW4064 is a small molecule known to be an agonist of the nuclear farnesoid X receptor (FXR). We found that GW4064 inhibits the NLR family CARD domain containing 3 (NLRP3) inflammasome activation in an FXR-independent manner as evidenced by its similar inhibitory effect on NLRP3 inflammasome activation in FXR-deficient macrophages. Interestingly, GW4064 decreases the nigericin-induced oligomerization and ubiquitination of ASC which is critical for the NLRP3 inflammasome activation. In vivo results indicate that GW4064 could partially rescue the symptoms of NLRP3-dependent inflammatory disease models. These results not only necessitate cautious interpretation of the biological function of GW4064 as an FXR agonist, but also provide a potential therapeutic approach using GW4064 in the treatment of NLRP3-related diseases. |
