Beyond the Toll-Like Receptor 4. Structure-Dependent Lipopolysaccharide Recognition Systems: How far are we?

IF 3.6 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-01-03 DOI:10.1002/cmdc.202400780
Stefania De Chiara, Luca De Simone Carone, Roberta Cirella, Dr. Emanuela Andretta, Prof. Alba Silipo, Prof. Antonio Molinaro, Dr. Marcello Mercogliano, Prof. Flaviana Di Lorenzo
{"title":"Beyond the Toll-Like Receptor 4. Structure-Dependent Lipopolysaccharide Recognition Systems: How far are we?","authors":"Stefania De Chiara,&nbsp;Luca De Simone Carone,&nbsp;Roberta Cirella,&nbsp;Dr. Emanuela Andretta,&nbsp;Prof. Alba Silipo,&nbsp;Prof. Antonio Molinaro,&nbsp;Dr. Marcello Mercogliano,&nbsp;Prof. Flaviana Di Lorenzo","doi":"10.1002/cmdc.202400780","DOIUrl":null,"url":null,"abstract":"<p>With an enormous potential in immunology and vaccinology, lipopolysaccharides (LPSs) are among the most extensively studied bacteria-derived molecules. LPS centered studies are countless, and their results reverberate in all areas of the life sciences, including chemistry, biology, genetics, biophysics, and medicine. Most of these research activities are focused on the LPS-induced immune response activation by means of Myeloid Differentiation protein-2/Toll Like Receptor 4 (MD-2/TLR4) complex, which currently is the most largely explored LPS sensing pathway. However, the enormous structural variability of LPS allows interactions with numerous other receptors involved in a wide range of equally important immunological scenarios. In this review, we explore these additional LPS recognition systems, which operate within interconnected signaling cascades, highlighting their role in maintaining physiological homeostasis and their involvement in the development of severe human diseases. Understanding these pathways, their interconnections, and the crosstalk between them and TLR4/MD-2 is essential for guiding the development of pharmacologically active molecules that could specifically modulate the inflammatory response, paving the way to new strategies for combating immune-mediated diseases and resistant infections.</p>","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 6","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202400780","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ChemMedChem","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cmdc.202400780","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

With an enormous potential in immunology and vaccinology, lipopolysaccharides (LPSs) are among the most extensively studied bacteria-derived molecules. LPS centered studies are countless, and their results reverberate in all areas of the life sciences, including chemistry, biology, genetics, biophysics, and medicine. Most of these research activities are focused on the LPS-induced immune response activation by means of Myeloid Differentiation protein-2/Toll Like Receptor 4 (MD-2/TLR4) complex, which currently is the most largely explored LPS sensing pathway. However, the enormous structural variability of LPS allows interactions with numerous other receptors involved in a wide range of equally important immunological scenarios. In this review, we explore these additional LPS recognition systems, which operate within interconnected signaling cascades, highlighting their role in maintaining physiological homeostasis and their involvement in the development of severe human diseases. Understanding these pathways, their interconnections, and the crosstalk between them and TLR4/MD-2 is essential for guiding the development of pharmacologically active molecules that could specifically modulate the inflammatory response, paving the way to new strategies for combating immune-mediated diseases and resistant infections.

Abstract Image

在toll样受体之外。结构依赖性脂多糖识别系统:我们走了多远?
脂多糖(lps)是研究最广泛的细菌衍生分子之一,在免疫学和疫苗学方面具有巨大的潜力。以脂多糖为中心的研究数不胜数,其结果在生命科学的各个领域都有反响,包括化学、生物学、遗传学、生物物理学和医学。这些研究活动大多集中在通过髓样分化蛋白-2/Toll样受体4 (MD-2/TLR4)复合物激活LPS诱导的免疫反应,这是目前探索最多的LPS感知途径。然而,LPS的巨大结构变异性允许与许多其他受体相互作用,这些受体参与了广泛的同样重要的免疫场景。在这篇综述中,我们探讨了这些额外的LPS识别系统,它们在相互连接的信号级联中运作,强调了它们在维持生理稳态和参与严重人类疾病发展中的作用。了解这些通路、它们之间的相互联系以及它们与TLR4/MD-2之间的串扰对于指导能够特异性调节炎症反应的药理活性分子的开发至关重要,为对抗免疫介导疾病和耐药感染的新策略铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信