Structures of Leukotriene Biosynthetic Enzymes and Development of New Therapeutics.

IF 11.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI:10.1146/annurev-pharmtox-051921-085014
Jesper Z Haeggström, Marcia E Newcomer
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引用次数: 7

Abstract

Leukotrienes are potent immune-regulating lipid mediators with patho-genic roles in inflammatory and allergic diseases, particularly asthma. These autacoids also contribute to low-grade inflammation, a hallmark of cardiovascular, neurodegenerative, metabolic, and tumor diseases. Biosynthesis of leukotrienes involves release and oxidative metabolism of arachidonic acid and proceeds via a set of cytosolic and integral membrane enzymes that are typically expressed by cells of the innate immune system. In activated cells, these enzymes traffic and assemble at the endoplasmic and perinuclear membrane, together comprising a biosynthetic complex. Here we describe recent advances in our molecular understanding of the protein components of the leukotriene-synthesizing enzyme machinery and also briefly touch upon the leukotriene receptors. Moreover, we discuss emerging opportunities for pharmacological intervention and development of new therapeutics.

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白三烯生物合成酶的结构及新疗法的研究进展。
白三烯是一种有效的免疫调节脂质介质,在炎症和过敏性疾病,特别是哮喘中具有致病作用。这些类自身物质也会导致低度炎症,这是心血管、神经退行性、代谢和肿瘤疾病的标志。白三烯的生物合成涉及花生四烯酸的释放和氧化代谢,并通过一组胞质和整体膜酶进行,这些酶通常由先天免疫系统的细胞表达。在活化的细胞中,这些酶在内质膜和核周膜上运输和组装,共同组成生物合成复合物。在这里,我们描述了在白三烯合成酶机制的蛋白质成分的分子理解的最新进展,并简要地谈到了白三烯受体。此外,我们讨论了药理学干预和新疗法发展的新机会。
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来源期刊
CiteScore
27.80
自引率
0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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