Mechanisms of NLRP3 activation and inhibition elucidated by functional analysis of disease-associated variants
The University of Melbourne · Walter and Eliza Hall Institute of Medical Research · +12 more institutions
Abstract
The NLRP3 inflammasome is a multiprotein complex that mediates caspase-1 activation and the release of proinflammatory cytokines, including interleukin (IL)-1β and IL-18. Gain-of-function variants in the gene encoding NLRP3 (also called cryopyrin) lead to constitutive inflammasome activation and excessive IL-1β production in cryopyrin-associated periodic syndromes (CAPS). Here we present functional screening and automated analysis of 534 NLRP3 variants from the international INFEVERS registry and the ClinVar database. This resource captures the effect of NLRP3 variants on ASC speck formation spontaneously, at low temperature, after inflammasome stimulation and with the specific NLRP3 inhibitor MCC950. Most…
Citation impact
- FWCI
- 41.90
- Percentile
- 100%
- References
- 84
Authors
18- SFShouya FengCorresponding
The University of Melbourne, Walter and Eliza Hall Institute of Medical Research, Hudson Institute of Medical Research, Monash University
- MCMatthew C Wierzbowski
The University of Melbourne, Walter and Eliza Hall Institute of Medical Research
- KHKatja Hrovat-Schaale
The University of Melbourne, Walter and Eliza Hall Institute of Medical Research
- ADAndreas Dumortier
The University of Melbourne, Walter and Eliza Hall Institute of Medical Research
- YZYaoyuan Zhang
The University of Melbourne, Walter and Eliza Hall Institute of Medical Research
Topics & keywords
- Disease
- Biology
- Genetics
- Computational biology
- Medicine
- Internal medicine