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

January 26th, 2015 by Huw D Lewis

Nature Chemical Biology 11, 189 (2015). doi:10.1038/nchembio.1735

Authors: Huw D Lewis, John Liddle, Jim E Coote, Stephen J Atkinson, Michael D Barker, Benjamin D Bax, Kevin L Bicker, Ryan P Bingham, Matthew Campbell, Yu Hua Chen, Chun-wa Chung, Peter D Craggs, Rob P Davis, Dirk Eberhard, Gerard Joberty, Kenneth E Lind, Kelly Locke, Claire Maller, Kimberly Martinod, Chris Patten, Oxana Polyakova, Cecil E Rise, Martin RĂ¼diger, Robert J Sheppard, Daniel J Slade, Pamela Thomas, Jim Thorpe, Gang Yao, Gerard Drewes, Denisa D Wagner, Paul R Thompson, Rab K Prinjha & David M Wilson

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.

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