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

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 critica...

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Detalles Bibliográficos
Autores principales: 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., Wilson, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397581/
https://www.ncbi.nlm.nih.gov/pubmed/25622091
http://dx.doi.org/10.1038/nchembio.1735
Descripción
Sumario: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.

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