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Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation

Lewis, Huw D., Liddle, John, Coote, Jim E., Atkinson, Stephen J., Barker, Michael D., Bax, Benjamin D., Bicker, Kevin L., Bingham, Ryan P., Campbell, Matthew, Chen, Yu Hua, Chung, Chun-wa, Craggs, Peter D., Davis, Rob P., Eberhard, Dirk, Joberty, Gerard, Lind, Kenneth E., Locke, Kelly, Maller, Claire, Martinod, Kimberly, Patten, Chris, Polyakova, Oxana, Rise, Cecil E, Rüdiger, Martin, Sheppard, Robert J., Slade, Daniel J., Thomas, Pamela, Thorpe, Jim, Yao, Gang, Drewes, Gerard, Wagner, Denisa D., Thompson, Paul R., Prinjha, Rab K. and Wilson, David M. 2015. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nature Chemical Biology 11 (3) , pp. 189-191. 10.1038/nchembio.1735

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Abstract

PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation for, to our knowledge, the first time. The therapeutic potential of PAD4 inhibitors can now be explored.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Nature Publishing Group
ISSN: 1552-4450
Date of Acceptance: 1 December 2014
Last Modified: 12 Mar 2019 13:59
URI: http://orca.cardiff.ac.uk/id/eprint/111273

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