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The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders.

ABSTRACT: Leukotrienes (LTs) are lipid mediators that play pivotal roles in acute and chronic inflammation and allergic diseases. They exert their biological effects by binding to specific G-protein-coupled receptors. Each LT receptor subtype exhibits unique functions and expression patterns. LTs play roles in various allergic diseases, including asthma (neutrophilic asthma and aspirin-sensitive asthma), allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and anaphylaxis. This review summarizes the biology of LTs and their receptors, recent developments in the area of anti-LT strategies (in settings such as ongoing clinical studies), and prospects for future therapeutic applications.

SUBMITTER: Jo-Watanabe A

PROVIDER: S-EPMC6679143 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders.

Jo-Watanabe Airi A Okuno Toshiaki T Yokomizo Takehiko T

International journal of molecular sciences 20190722 14

Leukotrienes (LTs) are lipid mediators that play pivotal roles in acute and chronic inflammation and allergic diseases. They exert their biological effects by binding to specific G-protein-coupled receptors. Each LT receptor subtype exhibits unique functions and expression patterns. LTs play roles in various allergic diseases, including asthma (neutrophilic asthma and aspirin-sensitive asthma), allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and anaphylaxis. This review summarizes ...[more]

PMID: 31336653

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Project description:G protein coupled receptors (GPCRs) were first characterized as signal transducers that elicit downstream effects through modulation of guanine (G) nucleotide-binding proteins. The pharmacotherapeutic exploitation of this signaling paradigm has created a drug-based field covering nearly 50% of the current pharmacopeia. Since the groundbreaking discoveries of the late 1990s to the present day, it is now clear however that GPCRs can also generate productive signaling cascades through the modulation of ?-arrestin functionality. ?-Arrestins were first thought to only regulate receptor desensitization and internalization - exemplified by the action of visual arrestin with respect to rhodopsin desensitization. Nearly 20 years ago, it was found that rather than controlling GPCR signal termination, productive ?-arrestin dependent GPCR signaling paradigms were highly dependent on multi-protein complex formation and generated long-lasting cellular effects, in contrast to G protein signaling which is transient and functions through soluble second messenger systems. ?-Arrestin signaling was then first shown to activate mitogen activated protein kinase signaling in a G protein-independent manner and eventually initiate protein transcription - thus controlling expression patterns of downstream proteins. While the possibility of developing ?-arrestin biased or functionally selective ligands is now being investigated, no additional research has been performed on its possible contextual specificity in treating age-related disorders. The ability of ?-arrestin-dependent signaling to control complex and multidimensional protein expression patterns makes this therapeutic strategy feasible, as treating complex age-related disorders will likely require therapeutics that can exert network-level efficacy profiles. It is our understanding that therapeutically targeting G protein-independent effectors such as ?-arrestin will aid in the development of precision medicines with tailored efficacy profiles for disease/age-specific contextualities.

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Dataset Information

The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders.

Publications

The Role of Leukotrienes as Potential Therapeutic Targets in Allergic Disorders.

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