Pharmacological targeting of adaptor proteins in chronic inflammation.

IF 4.8 3区 医学 Q2 CELL BIOLOGY Inflammation Research Pub Date : 2024-10-01 Epub Date: 2024-07-25 DOI:10.1007/s00011-024-01921-5
Shubhi Raizada, Alexander G Obukhov, Shreya Bharti, Khandu Wadhonkar, Mirza S Baig
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Abstract

Background: Inflammation, a biological response of the immune system, can be triggered by various factors such as pathogens, damaged cells, and toxic compounds. These factors can lead to chronic inflammatory responses, potentially causing tissue damage or disease. Both infectious and non-infectious agents, as well as cell damage, activate inflammatory cells and trigger common inflammatory signalling pathways, including NF-κB, MAPK, and JAK-STAT pathways. These pathways are activated through adaptor proteins, which possess distinct protein binding domains that connect corresponding interacting molecules to facilitate downstream signalling. Adaptor molecules have gained widespread attention in recent years due to their key role in chronic inflammatory diseases.

Methods: In this review, we explore potential pharmacological agents that can be used to target adaptor molecules in chronic inflammatory responses. A comprehensive analysis of published studies was performed to obtain information on pharmacological agents.

Conclusion: This review highlights the therapeutic strategies involving small molecule inhibitors, antisense oligonucleotide therapy, and traditional medicinal compounds that have been found to inhibit the inflammatory response and pro-inflammatory cytokine production. These strategies primarily block the protein-protein interactions in the inflammatory signaling cascade. Nevertheless, extensive preclinical studies and risk assessment methodologies are necessary to ensure their safety.

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慢性炎症中适应蛋白的药理靶标。
背景:炎症是免疫系统的一种生物反应,可由病原体、受损细胞和有毒化合物等各种因素引发。这些因素会导致慢性炎症反应,可能造成组织损伤或疾病。感染性和非感染性病原体以及细胞损伤都会激活炎症细胞并触发常见的炎症信号通路,包括 NF-κB、MAPK 和 JAK-STAT 通路。这些途径是通过适配蛋白激活的,适配蛋白具有不同的蛋白结合域,可连接相应的相互作用分子,促进下游信号传导。近年来,适配体分子因其在慢性炎症性疾病中的关键作用而受到广泛关注:在这篇综述中,我们探讨了在慢性炎症反应中可用于靶向适配体分子的潜在药理制剂。我们对已发表的研究进行了全面分析,以获取有关药理制剂的信息:本综述重点介绍了涉及小分子抑制剂、反义寡核苷酸疗法和传统药用化合物的治疗策略,这些策略已被发现可抑制炎症反应和促炎症细胞因子的产生。这些策略主要是阻断炎症信号级联中蛋白质与蛋白质之间的相互作用。然而,为了确保其安全性,有必要进行广泛的临床前研究和风险评估方法。
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来源期刊
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
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