Leukotriene biosynthetic enzymes as therapeutic targets

被引：125

作者：

Haeggstrom, Jesper Z. ^{[1
]}

机构：

[1] Karolinska Inst, Dept Med Biochem & Biophys, Div Chem 2, S-17177 Stockholm, Sweden

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2018年 / 128卷 / 07期

基金：

瑞典研究理事会;

关键词：

5-LIPOXYGENASE-ACTIVATING PROTEIN FLAP; GLUTATHIONE-S-TRANSFERASE; C-4 SYNTHASE EXPRESSION; A(4) HYDROLASE; PULMONARY-HYPERTENSION; INSULIN-RESISTANCE; CRYSTAL-STRUCTURE; ARACHIDONIC-ACID; LIPID MEDIATORS; A4; HYDROLASE;

D O I：

10.1172/JCI97945

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Leukotrienes are powerful immune-regulating lipid mediators with established pathogenic roles in inflammatory allergic diseases of the respiratory tract - in particular, asthma and hay fever. More recent work indicates that these lipids also contribute to low-grade inflammation, a hallmark of cardiovascular, neurodegenerative, and metabolic diseases as well as cancer. Biosynthesis of leukotrienes involves oxidative metabolism of arachidonic acid and proceeds via a set of soluble and membrane enzymes that are primarily expressed by cells of myeloid origin. In activated immune cells, these enzymes assemble at the endoplasmic and perinuclear membrane, constituting a biosynthetic complex. This Review describes recent advances in our understanding of the components of the leukotriene-synthesizing enzyme machinery, emerging opportunities for pharmacological intervention, and the development of new medicines exploiting both antiinflammatory and pro-resolving mechanisms.

引用

页码：2680 / 2690

页数：11

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