对非典型炎性体的新见解指出caspase-4是一种可药物靶标

IF 67.7 1区医学 Q1 IMMUNOLOGY

Nature Reviews Immunology Pub Date : 2025-03-05 DOI:10.1038/s41577-025-01142-9

Elad Elkayam, Francois G. Gervais, Hao Wu, Michael A. Crackower, Judy Lieberman

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引用次数: 0

摘要

最近的研究表明，人脂多糖传感器caspase-4与其小鼠同源caspase-11不同，它是组成性表达的，并激活亲il -18和气皮蛋白d介导的焦亡。人caspase-4的激活导致小鼠全身和血脑屏障的血管渗漏，并与一系列炎症性疾病的发病机制有关，目前尚无有效的治疗方法。这些结果表明调节caspase-4活性的治疗潜力，结构研究表明caspase-4外源可能是一个有希望的抑制靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

New insights into the noncanonical inflammasome point to caspase-4 as a druggable target

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New insights into the noncanonical inflammasome point to caspase-4 as a druggable target

Recent studies indicate that the human lipopolysaccharide sensor caspase-4, unlike its mouse homologue caspase-11, is constitutively expressed and activates pro-IL-18 as well as gasdermin D-mediated pyroptosis. Activation of human caspase-4 causes vascular leakage systemically and at the blood–brain barrier in mice and is implicated in the pathogenesis of a range of inflammatory diseases for which there are currently no effective therapies. These results suggest the therapeutic potential of modulating caspase-4 activity, and structural studies indicate that the caspase-4 exosite might be a promising inhibitory target.

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来源期刊

Nature Reviews Immunology 医学-免疫学

CiteScore

93.40

自引率

0.40%

发文量

131

审稿时长

6-12 weeks

期刊介绍： Nature Reviews Immunology is a journal that provides comprehensive coverage of all areas of immunology, including fundamental mechanisms and applied aspects. It has two international standard serial numbers (ISSN): 1474-1733 for print and 1474-1741 for online. In addition to review articles, the journal also features recent developments and new primary papers in the field, as well as reflections on influential people, papers, and events in the development of immunology. The subjects covered by Nature Reviews Immunology include allergy and asthma, autoimmunity, antigen processing and presentation, apoptosis and cell death, chemokines and chemokine receptors, cytokines and cytokine receptors, development and function of cells of the immune system, haematopoiesis, infection and immunity, immunotherapy, innate immunity, mucosal immunology and the microbiota, regulation of the immune response, signalling in the immune system, transplantation, tumour immunology and immunotherapy, and vaccine development.