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GPCR-dependent and -independent arrestin signaling. 依赖和不依赖 GPCR 的 arrestin 信号转导。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-07-01 Epub Date: 2024-06-20 DOI: 10.1016/j.tips.2024.05.007
Vsevolod V Gurevich, Eugenia V Gurevich
{"title":"GPCR-dependent and -independent arrestin signaling.","authors":"Vsevolod V Gurevich, Eugenia V Gurevich","doi":"10.1016/j.tips.2024.05.007","DOIUrl":"10.1016/j.tips.2024.05.007","url":null,"abstract":"<p><p>Biological activity of free arrestins is often overlooked. Based on available data, we compare arrestin-mediated signaling that requires and does not require binding to G-protein-coupled receptors (GPCRs). Receptor-bound arrestins activate ERK1/2, Src, and focal adhesion kinase (FAK). Yet, arrestin-3 regulation of Src family member Fgr does not appear to involve receptors. Free arrestin-3 facilitates the activation of JNK family kinases, preferentially binds E3 ubiquitin ligases Mdm2 and parkin, and facilitates parkin-dependent mitophagy. The binding of arrestins to microtubules and calmodulin and their function in focal adhesion disassembly and apoptosis also do not involve receptors. Biased GPCR ligands and the phosphorylation barcode can only affect receptor-dependent arrestin signaling. Thus, elucidation of receptor dependence or independence of arrestin functions has important scientific and therapeutic implications.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multi-target drugs for Alzheimer's disease. 治疗阿尔茨海默病的多靶点药物。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-07-01 Epub Date: 2024-06-09 DOI: 10.1016/j.tips.2024.05.005
Bengisu Turgutalp, Caghan Kizil
{"title":"Multi-target drugs for Alzheimer's disease.","authors":"Bengisu Turgutalp, Caghan Kizil","doi":"10.1016/j.tips.2024.05.005","DOIUrl":"10.1016/j.tips.2024.05.005","url":null,"abstract":"<p><p>Alzheimer's disease (AD), a leading cause of dementia, increasingly challenges our healthcare systems and society. Traditional therapies aimed at single targets have fallen short owing to the complex, multifactorial nature of AD that necessitates simultaneous targeting of various disease mechanisms for clinical success. Therefore, targeting multiple pathologies at the same time could provide a synergistic therapeutic effect. The identification of new disease targets beyond the classical hallmarks of AD offers a fertile ground for the design of new multi-target drugs (MTDs), and building on existing compounds have the potential to yield in successful disease modifying therapies. This review discusses the evolving landscape of MTDs, focusing on their potential as AD therapeutics. Analysis of past and current trials of compounds with multi-target activity underscores the capacity of MTDs to offer synergistic therapeutic effects, and the flourishing genetic understanding of AD will inform and inspire the development of MTD-based AD therapies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Artificial protein coronas: directing nanoparticles to targets. 人造蛋白质冠：将纳米粒子导向目标。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-07-01 Epub Date: 2024-05-28 DOI: 10.1016/j.tips.2024.05.003
Giulio Caracciolo
{"title":"Artificial protein coronas: directing nanoparticles to targets.","authors":"Giulio Caracciolo","doi":"10.1016/j.tips.2024.05.003","DOIUrl":"10.1016/j.tips.2024.05.003","url":null,"abstract":"<p><p>The protein corona surrounding nanoparticles (NPs) offers exciting possibilities for targeted drug delivery. However, realizing this potential requires direct evidence of corona-receptor interactions in vivo; a challenge hampered by the limitations of in vitro settings. This opinion proposes that utilizing engineered protein coronas can address this challenge. Artificial coronas made of selected plasma proteins retain their properties in vivo, enabling manipulation for specific receptor targeting. To directly assess corona-receptor interactions mimicking in vivo complexity, we propose testing artificial coronas with recently adapted quartz crystal microbalance (QCM) setups whose current limitations and potential advancements are critically discussed. Finally, the opinion proposes future experiments to decipher corona-receptor interactions and unlock the full potential of the protein corona for NP-based drug delivery.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advisory Board and Contents 咨询委员会和内容
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-06-06 DOI: 10.1016/s0165-6147(24)00104-4
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/s0165-6147(24)00104-4","DOIUrl":"https://doi.org/10.1016/s0165-6147(24)00104-4","url":null,"abstract":"No Abstract","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Subscription and Copyright Information 订阅和版权信息
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-06-06 DOI: 10.1016/s0165-6147(24)00108-1
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/s0165-6147(24)00108-1","DOIUrl":"https://doi.org/10.1016/s0165-6147(24)00108-1","url":null,"abstract":"No Abstract","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141511434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tackling therapy resistance in cancer. 应对癌症的抗药性
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-06-01 Epub Date: 2024-05-21 DOI: 10.1016/j.tips.2024.05.002
Jerry C Madukwe
{"title":"Tackling therapy resistance in cancer.","authors":"Jerry C Madukwe","doi":"10.1016/j.tips.2024.05.002","DOIUrl":"10.1016/j.tips.2024.05.002","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anticancer drugs: How to select small molecule combinations? 抗癌药物：如何选择小分子组合？
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-06-01 Epub Date: 2024-05-22 DOI: 10.1016/j.tips.2024.04.012
Ruth Nussinov, Bengi Ruken Yavuz, Hyunbum Jang
{"title":"Anticancer drugs: How to select small molecule combinations?","authors":"Ruth Nussinov, Bengi Ruken Yavuz, Hyunbum Jang","doi":"10.1016/j.tips.2024.04.012","DOIUrl":"10.1016/j.tips.2024.04.012","url":null,"abstract":"<p><p>Small molecules are at the forefront of anticancer therapies. Successive treatments with single molecules incur drug resistance, calling for combination. Here, we explore the tough choices oncologists face - not just which drugs to use but also the best treatment plans, based on factors such as target proteins, pathways, and gene expression. We consider the reality of cancer's disruption of normal cellular processes, highlighting why it's crucial to understand the ins and outs of current treatment methods. The discussion on using combination drug therapies to target multiple pathways sheds light on a promising approach while also acknowledging the hurdles that come with it, such as dealing with pathway crosstalk. We review options and provide examples and the mechanistic basis, altogether providing the first comprehensive guide to combinatorial therapy selection.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Emerging targets in lipid metabolism for cancer therapy. 用于癌症治疗的脂质代谢新目标。
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-06-01 Epub Date: 2024-05-17 DOI: 10.1016/j.tips.2024.04.007
Alexander R Terry, Nissim Hay
{"title":"Emerging targets in lipid metabolism for cancer therapy.","authors":"Alexander R Terry, Nissim Hay","doi":"10.1016/j.tips.2024.04.007","DOIUrl":"10.1016/j.tips.2024.04.007","url":null,"abstract":"<p><p>Cancer cells perturb lipid metabolic pathways for a variety of pro-tumorigenic functions, and deregulated cellular metabolism is a hallmark of cancer cells. Although alterations in lipid metabolism in cancer cells have been appreciated for over 20 years, there are no FDA-approved cancer treatments that target lipid-related pathways. Recent advances pertaining to cancer cell fatty acid synthesis (FAS), desaturation, and uptake, microenvironmental and dietary lipids, and lipid metabolism of tumor-infiltrating immune cells have illuminated promising clinical applications for targeting lipid metabolism. This review highlights emerging pathways and targets for tumor lipid metabolism that may soon impact clinical treatment.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Emerging paradigms and recent progress in targeting ErbB in cancers. 针对癌症中 ErbB 的新模式和最新进展。
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-06-01 Epub Date: 2024-05-25 DOI: 10.1016/j.tips.2024.04.009
Nicolas Stoup, Maxime Liberelle, Nicolas Lebègue, Isabelle Van Seuningen
{"title":"Emerging paradigms and recent progress in targeting ErbB in cancers.","authors":"Nicolas Stoup, Maxime Liberelle, Nicolas Lebègue, Isabelle Van Seuningen","doi":"10.1016/j.tips.2024.04.009","DOIUrl":"10.1016/j.tips.2024.04.009","url":null,"abstract":"<p><p>The epidermal growth factor receptor (EGFR) family is a class of transmembrane proteins, highly regarded as anticancer targets due to their pivotal role in various malignancies. Standard cancer treatments targeting the ErbB receptors include tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs). Despite their substantial survival benefits, the achievement of curative outcomes is hindered by acquired resistance. Recent advancements in anti-ErbB approaches, such as inhibitory peptides, nanobodies, targeted-protein degradation strategies, and bispecific antibodies (BsAbs), aim to overcome such resistance. More recently, emerging insights into the cell surface interactome of the ErbB family open new avenues for modulating ErbB signaling by targeting specific domains of ErbB partners. Here, we review recent progress in ErbB targeting and elucidate emerging paradigms that underscore the significance of EGF domain-containing proteins (EDCPs) as new ErbB-targeting pathways.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Directions to overcome therapy resistance in cancer. 克服癌症抗药性的方向
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-06-01 Epub Date: 2024-05-16 DOI: 10.1016/j.tips.2024.05.001
Ruth Nussinov, Thomas Weichhart, Zodwa Dlamini, Don L Gibbons, Isabelle Van Seuningen, Jessica Konen, Huai-Qiang Ju
{"title":"Directions to overcome therapy resistance in cancer.","authors":"Ruth Nussinov, Thomas Weichhart, Zodwa Dlamini, Don L Gibbons, Isabelle Van Seuningen, Jessica Konen, Huai-Qiang Ju","doi":"10.1016/j.tips.2024.05.001","DOIUrl":"10.1016/j.tips.2024.05.001","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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