Identification of NLRP3PYD Homo-Oligomerization Inhibitors with Anti-Inflammatory Activity

Simple item page
dc.contributor.authorGhafary, Soroush Moasses
dc.contributor.authorSoriano-Teruel, Paula M.
dc.contributor.authorKarami, Fatemeh
dc.contributor.authorBarigye, Stephen J.
dc.contributor.authorFernández-Pérez, Iván
dc.date.accessioned2023-02-09T17:59:23Z
dc.date.available2023-02-09T17:59:23Z
dc.date.issued2022
dc.description.abstractInflammasomes are multiprotein complexes that represent critical elements of the inflammatory response. The dysregulation of the best-characterized complex, the NLRP3 inflammasome, has been linked to the pathogenesis of diseases such as multiple sclerosis, type 2 diabetes mellitus, Alzheimer’s disease, and cancer. While there exist molecular inhibitors specific for the various components of inflammasome complexes, no currently reported inhibitors specifically target NLRP3PYD homo-oligomerization. In the present study, we describe the identification of QM380 and QM381 as NLRP3PYD homo-oligomerization inhibitors after screening small molecules from the MyriaScreen library using a split-luciferase complementation assay. Our results demonstrate that these NLRP3PYD inhibitors interfere with ASC speck formation, inhibit pro-inflammatory cytokine IL1-β release, and decrease pyroptotic cell death. We employed spectroscopic techniques and computational docking analyses with QM380 and QM381 and the PYD domain to confirm the experimental results and predict possible mechanisms underlying the inhibition of NLRP3PYD homo-interactions.en_US
dc.identifier.citationMoasses Ghafary, S., Soriano-Teruel, P. M., Lotfollahzadeh, S., Sancho, M., Serrano-Candelas, E., Karami, F., ... & Hosseinkhani, S. (2022). Identification of NLRP3PYD Homo-Oligomerization Inhibitors with Anti-Inflammatory Activity. International Journal of Molecular Sciences, 23(3), 1651.https://doi.org/10.3390/ijms23031651en_US
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/7719
dc.language.isoenen_US
dc.publisherInternational Journal of Molecular Sciencesen_US
dc.subjectinflammasome inhibitorsen_US
dc.subjectNLRP3en_US
dc.subjectscreeningen_US
dc.subjectsplit-luciferaseen_US
dc.subjectpyroptosisen_US
dc.titleIdentification of NLRP3PYD Homo-Oligomerization Inhibitors with Anti-Inflammatory Activityen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Identification of NLRP3PYD Homo-Oligomerization Inhibitors with Anti-Inflammatory Activity.pdf
Size:
3.97 MB
Format:
Adobe Portable Document Format
Description:
Identification of NLRP3PYD Homo-Oligomerization Inhibitors with Anti-Inflammatory Activity
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Engineering and Technology