Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation
By H. Lewis, J. Liddle, J. Coote, S. Atkinson, M. Barker, B. Bax, Kevin L. Bicker, Ryan P. Bingham, M. Campbell, Yu Hua Chen and 23 more. Nature Chemical Biology, 2015
716 citations recorded by the source corpus.
PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases, through clinical genetics and gene disruption in mice. Novel, selective PAD4 inhibitors binding to a calcium-deficient form of the PAD4 enzyme have, for the first time, validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation. The therapeutic potential of PAD4 inhibitors can now be explored.
Subfields: Cancer Research, Immunology, Immunology and Allergy
View Paper: https://www.semanticscholar.org/paper/8a9837801dff8fa772d36c323b4bedcaf75e8f12
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In Immunology
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In Immunology and Allergy
Citations in the corpus
- Diverse stimuli engage different neutrophil extracellular trap pathways (2017, background): “Importantly, studies examining the requirements of the PAD enzymes in human NETosis, using the same PAD inhibitors, also demonstrate a very limited inhibition of NETosis in response to a calcium ionophore and S. aureus (Hosseinzadeh et al., 2016; Lewis et al., 2015).”
- Cellular and molecular mechanisms of skin wound healing (2024, neutral): “…is achieved by a combination of targeted ROS release and the formation of NETs (by release of their DNA into the extracellular space), in combination with antimicrobial molecules, in a process which is dependent on neutrophil elastase, peptidylarginine deaminase 4 (PAD4) and gasdermin D 86–89 (Fig.”
- Neutrophil Extracellular Traps and Its Implications in Inflammation: An Overview (2017, background): “Suicidal NETosis is dependent on ROS for histone citrullination by PAD4, which allows chromatin decondensation (16, 17, 19), finally releasing the DNA as extracellular traps (ETs) (Figure 1) (20, 21).”