Chemical modulation of gasdermin D activity: Therapeutic implications and consequences

IF 7.4 2区 医学 Q1 IMMUNOLOGY Seminars in Immunology Pub Date : 2023-10-08 DOI:10.1016/j.smim.2023.101845
Bowen Zhou, Derek W. Abbott
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Abstract

The gasdermin family of proteins are central effectors of the inflammatory, lytic cell death modality known as pyroptosis. Characterized in 2015, the most well-studied member gasdermin D can be proteolyzed, typically by caspases, to generate an active pore-forming N-terminal domain. At least well-studied three pharmacological inhibitors (necrosulfonamide, disulfiram, dimethyl fumarate) since 2018 have been shown to affect gasdermin D activity either through modulation of processing or interference with pore formation. A multitude of murine in vivo studies have since followed. Here, we discuss the current state of research surrounding these three inhibitors, caveats to their use, and a set of guiding principles that researchers should consider when pursuing further studies of gasdermin D inhibition.

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gasdermin D活性的化学调节:治疗意义和后果。
gasdermin蛋白家族是炎症性、裂解性细胞死亡模式(pyroptosis)的中心效应物。2015年,研究最深入的成员gasdermin D可以进行蛋白水解,通常通过半胱天冬酶进行,以产生活性的成孔N-末端结构域。自2018年以来,至少有三种经过充分研究的药理学抑制剂(坏死磺酰胺、二硫仑、富马酸二甲酯)已被证明通过调节加工或干扰孔隙形成来影响gasdermin D的活性。此后进行了大量的小鼠体内研究。在这里,我们讨论了围绕这三种抑制剂的研究现状,它们的使用注意事项,以及研究人员在进一步研究gasdermin D抑制作用时应考虑的一套指导原则。
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来源期刊
Seminars in Immunology
Seminars in Immunology 医学-免疫学
CiteScore
11.40
自引率
1.30%
发文量
50
审稿时长
89 days
期刊介绍: Seminars in Immunology is a specialized review journal that serves as a valuable resource for scientists in the field of immunology. The journal's approach is thematic, with each issue dedicated to a specific topic of significant interest to immunologists. It covers a wide range of research areas, from the molecular and cellular foundations of the immune response to the potential for its manipulation, highlighting recent advancements in these areas. Each thematic issue is curated by a guest editor, who is recognized as an expert in the field internationally. The content of each issue typically includes six to eight authoritative invited reviews, which delve into various aspects of the chosen topic. The goal of these reviews is to provide a comprehensive, coherent, and engaging overview of the subject matter, ensuring that the information is presented in a timely manner to maintain its relevance. The journal's commitment to quality and timeliness is further supported by its inclusion in the Scopus database, which is a leading abstract and citation database of peer-reviewed literature. Being indexed in Scopus helps to ensure that the journal's content is accessible to a broad audience of researchers and professionals in immunology and related fields.
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