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抑制肽瓜氨酸脱氨酶4（PAD4）的活性足以破坏小鼠和人类中性粒细胞胞外陷阱（NET）的形成。

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

作者信息

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

机构信息

EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.

Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.

出版信息

Nat Chem Biol. 2015 Mar;11(3):189-91. doi: 10.1038/nchembio.1735. Epub 2015 Jan 26.

DOI:10.1038/nchembio.1735
PMID:25622091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4397581/
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.

摘要

通过临床遗传学和小鼠基因敲除研究，肽基精氨酸脱亚氨酶4（PAD4）与自身免疫性疾病、心血管疾病及肿瘤疾病的发病机制密切相关。新型选择性PAD4抑制剂可与缺乏钙的PAD4酶形式结合，据我们所知，这首次证实了人和小鼠PAD4在组蛋白瓜氨酸化及中性粒细胞胞外诱捕网形成过程中的关键酶作用。现在可以探索PAD4抑制剂的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac29/4397581/e7e302c92e61/nihms646216f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac29/4397581/0e5b4bedb166/nihms646216f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac29/4397581/3eb06e83355f/nihms646216f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac29/4397581/e7e302c92e61/nihms646216f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac29/4397581/0e5b4bedb166/nihms646216f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac29/4397581/3eb06e83355f/nihms646216f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac29/4397581/e7e302c92e61/nihms646216f3.jpg

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