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

HD Lewis, J Liddle, JE Coote, SJ Atkinson… - Nature chemical …, 2015 - nature.com
HD Lewis, J Liddle, JE Coote, SJ Atkinson, MD Barker, BD Bax, KL Bicker, RP Bingham…
Nature chemical biology, 2015nature.com
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.
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.
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