Target of MCC950 in Inhibition of NLRP3 Inflammasome Activation: a Literature Review
MCC950 has been proposed as a specific small molecule inhibitor that can selectively block NLRP3 inflammasome activation. However, the exact mechanism of its action is still ambiguous. Accumulating investigations imply that chloride efflux–dependent ASC speck oligomerization and potassium efflux–dep...
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| Published in | Inflammation Vol. 43; no. 1; pp. 17 - 23 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
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New York
Springer US
01.02.2020
Springer Nature B.V |
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| Abstract | MCC950 has been proposed as a specific small molecule inhibitor that can selectively block NLRP3 inflammasome activation. However, the exact mechanism of its action is still ambiguous. Accumulating investigations imply that chloride efflux–dependent ASC speck oligomerization and potassium efflux–dependent activation of caspase-1 are the two relatively independent, but indispensable events for NLRP3 inflammasome activation. Previous studies suggested that influence of MCC950 on potassium efflux and its consequent events such as interaction between NEK7 and NLRP3 are limited. However, inhibiting chloride intracellular channel–dependent chloride efflux leads to a modification of inflammatory response, which is similar to the function of MCC950. Based on these findings, we shed new insights on the understanding of MCC950 that its function might correlate with chloride efflux, chloride intracellular channels, or other targets that act upstream of chloride efflux. |
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| AbstractList | MCC950 has been proposed as a specific small molecule inhibitor that can selectively block NLRP3 inflammasome activation. However, the exact mechanism of its action is still ambiguous. Accumulating investigations imply that chloride efflux-dependent ASC speck oligomerization and potassium efflux-dependent activation of caspase-1 are the two relatively independent, but indispensable events for NLRP3 inflammasome activation. Previous studies suggested that influence of MCC950 on potassium efflux and its consequent events such as interaction between NEK7 and NLRP3 are limited. However, inhibiting chloride intracellular channel-dependent chloride efflux leads to a modification of inflammatory response, which is similar to the function of MCC950. Based on these findings, we shed new insights on the understanding of MCC950 that its function might correlate with chloride efflux, chloride intracellular channels, or other targets that act upstream of chloride efflux.MCC950 has been proposed as a specific small molecule inhibitor that can selectively block NLRP3 inflammasome activation. However, the exact mechanism of its action is still ambiguous. Accumulating investigations imply that chloride efflux-dependent ASC speck oligomerization and potassium efflux-dependent activation of caspase-1 are the two relatively independent, but indispensable events for NLRP3 inflammasome activation. Previous studies suggested that influence of MCC950 on potassium efflux and its consequent events such as interaction between NEK7 and NLRP3 are limited. However, inhibiting chloride intracellular channel-dependent chloride efflux leads to a modification of inflammatory response, which is similar to the function of MCC950. Based on these findings, we shed new insights on the understanding of MCC950 that its function might correlate with chloride efflux, chloride intracellular channels, or other targets that act upstream of chloride efflux. MCC950 has been proposed as a specific small molecule inhibitor that can selectively block NLRP3 inflammasome activation. However, the exact mechanism of its action is still ambiguous. Accumulating investigations imply that chloride efflux-dependent ASC speck oligomerization and potassium efflux-dependent activation of caspase-1 are the two relatively independent, but indispensable events for NLRP3 inflammasome activation. Previous studies suggested that influence of MCC950 on potassium efflux and its consequent events such as interaction between NEK7 and NLRP3 are limited. However, inhibiting chloride intracellular channel-dependent chloride efflux leads to a modification of inflammatory response, which is similar to the function of MCC950. Based on these findings, we shed new insights on the understanding of MCC950 that its function might correlate with chloride efflux, chloride intracellular channels, or other targets that act upstream of chloride efflux. AbstractMCC950 has been proposed as a specific small molecule inhibitor that can selectively block NLRP3 inflammasome activation. However, the exact mechanism of its action is still ambiguous. Accumulating investigations imply that chloride efflux–dependent ASC speck oligomerization and potassium efflux–dependent activation of caspase-1 are the two relatively independent, but indispensable events for NLRP3 inflammasome activation. Previous studies suggested that influence of MCC950 on potassium efflux and its consequent events such as interaction between NEK7 and NLRP3 are limited. However, inhibiting chloride intracellular channel–dependent chloride efflux leads to a modification of inflammatory response, which is similar to the function of MCC950. Based on these findings, we shed new insights on the understanding of MCC950 that its function might correlate with chloride efflux, chloride intracellular channels, or other targets that act upstream of chloride efflux. |
| Author | Wang, Yangxue Jiang, Xijuan Wu, Danbin Gao, Qing Chen, Yefei Li, Huhu Yu, Bin Sun, Yingxin Yang, Zhengfei |
| Author_xml | – sequence: 1 givenname: Danbin surname: Wu fullname: Wu, Danbin organization: School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine – sequence: 2 givenname: Yefei surname: Chen fullname: Chen, Yefei organization: School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine – sequence: 3 givenname: Yingxin surname: Sun fullname: Sun, Yingxin organization: School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine – sequence: 4 givenname: Qing surname: Gao fullname: Gao, Qing organization: School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine – sequence: 5 givenname: Huhu surname: Li fullname: Li, Huhu organization: School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine – sequence: 6 givenname: Zhengfei surname: Yang fullname: Yang, Zhengfei organization: School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine – sequence: 7 givenname: Yangxue surname: Wang fullname: Wang, Yangxue organization: School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine – sequence: 8 givenname: Xijuan surname: Jiang fullname: Jiang, Xijuan email: xijuanjiang@foxmail.com organization: School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine – sequence: 9 givenname: Bin surname: Yu fullname: Yu, Bin email: yubin_771115@hotmail.com organization: International Exchanges Department & International Education College, Tianjin University of Traditional Chinese Medicine |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31646445$$D View this record in MEDLINE/PubMed |
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| Snippet | MCC950 has been proposed as a specific small molecule inhibitor that can selectively block NLRP3 inflammasome activation. However, the exact mechanism of its... AbstractMCC950 has been proposed as a specific small molecule inhibitor that can selectively block NLRP3 inflammasome activation. However, the exact mechanism... |
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| SubjectTerms | Animals Anti-Inflammatory Agents - pharmacology Biomedical and Life Sciences Biomedicine Caspase-1 Chloride Chloride channels Heterocyclic Compounds, 4 or More Rings - pharmacology Humans Immunology Inflammasomes Inflammasomes - drug effects Inflammasomes - immunology Inflammasomes - metabolism Inflammation Inflammation - drug therapy Inflammation - immunology Inflammation - metabolism Internal Medicine Intracellular Literature reviews Molecular Targeted Therapy NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors NLR Family, Pyrin Domain-Containing 3 Protein - immunology NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Oligomerization Pathology Pharmacology/Toxicology Potassium Review Rheumatology Signal Transduction Sulfones - pharmacology |
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| Title | Target of MCC950 in Inhibition of NLRP3 Inflammasome Activation: a Literature Review |
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