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PANoptosis: a novel target for cardiovascular diseases. 泛凋亡：心血管疾病的新靶点。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-08-01 Epub Date: 2024-07-12 DOI: 10.1016/j.tips.2024.06.002
Qi Xiang, Zhen-Xi Geng, Xin Yi, Xiang Wei, Xue-Hai Zhu, Ding-Sheng Jiang
{"title":"PANoptosis: a novel target for cardiovascular diseases.","authors":"Qi Xiang, Zhen-Xi Geng, Xin Yi, Xiang Wei, Xue-Hai Zhu, Ding-Sheng Jiang","doi":"10.1016/j.tips.2024.06.002","DOIUrl":"10.1016/j.tips.2024.06.002","url":null,"abstract":"<p><p>PANoptosis is a unique innate immune inflammatory lytic cell death pathway initiated by an innate immune sensor and driven by caspases and RIPKs. As a distinct pathway, the execution of PANoptosis cannot be hindered by targeting other cell death pathways, such as pyroptosis, apoptosis, or necroptosis. Instead, targeting key PANoptosome components can serve as a strategy to prevent this form of cell death. Given the physiological relevance in several diseases, PANoptosis is a pivotal therapeutic target. Notably, previous research has primarily focused on the role of PANoptosis in cancer and infectious and inflammatory diseases. By contrast, its role in cardiovascular diseases has not been comprehensively discussed. Here, we review the available evidence on PANoptosis in cardiovascular diseases, including cardiomyopathy, atherosclerosis, myocardial infarction, myocarditis, and aortic aneurysm and dissection, and explore a variety of agents that target PANoptosis, with the overarching goal of providing a novel complementary approach to combatting cardiovascular diseases.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"739-756"},"PeriodicalIF":13.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604194","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
Advances in GPCR-targeted drug development in dermatology. 皮肤科 GPCR 靶向药物开发的进展。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-08-01 Epub Date: 2024-07-25 DOI: 10.1016/j.tips.2024.06.007
Meng Wang, Tao Zan, Chengang Fan, Zhouxiao Li, Danru Wang, Qingfeng Li, Chao Zhang
{"title":"Advances in GPCR-targeted drug development in dermatology.","authors":"Meng Wang, Tao Zan, Chengang Fan, Zhouxiao Li, Danru Wang, Qingfeng Li, Chao Zhang","doi":"10.1016/j.tips.2024.06.007","DOIUrl":"10.1016/j.tips.2024.06.007","url":null,"abstract":"<p><p>Achieving the efficacy and specificity of G-protein-coupled receptor (GPCR) targeting-drugs in the skin remains challenging. Understanding the molecular mechanism underlying GPCR dysfunction is crucial for developing targeted therapies. Recent advances in genetic, signal transduction, and structural studies have significantly improved our understanding of cutaneous GPCR functions in both normal and pathological states. In this review, we summarize recent discoveries of pathogenic GPCRs in dermal injuries, chronic inflammatory dermatoses, cutaneous malignancies, as well as the development of potent potential drugs. We also discuss targeting of cutaneous GPCR complexes via the transient receptor potential (TRP) channel and structure elucidation, which provide new opportunities for therapeutic targeting of GPCRs involved in skin disorders. These insights are expected to lead to more effective and specific treatments for various skin conditions.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"678-690"},"PeriodicalIF":13.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767485","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
BTK inhibitors: past, present, and future BTK 抑制剂：过去、现在和未来
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-07-17 DOI: 10.1016/j.tips.2024.06.006
{"title":"BTK inhibitors: past, present, and future","authors":"","doi":"10.1016/j.tips.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.tips.2024.06.006","url":null,"abstract":"<p>Bruton’s tyrosine kinase (BTK) inhibitors have revolutionized the treatment landscape for B cell lymphomas such as chronic lymphocytic leukemia (CLL). The first-in-class BTK inhibitor ibrutinib has recently been succeeded by covalent BTK inhibitors that are safer but still face challenges of resistance mutations. The noncovalent BTK inhibitor pirtobrutinib was recently approved for relapsed and refractory CLL, and whether noncovalent BTK inhibitors will supplant covalent BTK inhibitors as upfront treatment options either alone or in combination will be determined. Meanwhile, newer BTK inhibitors and BTK degraders are vying for their place in the potential future landscape of B cell cancers as well as autoimmune diseases. This review will cover the latest progress in BTK inhibitor development and where the field is moving in light of these recent discoveries.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":"307 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141721101","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 : 2024-07-05 DOI: 10.1016/s0165-6147(24)00130-5
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/s0165-6147(24)00130-5","DOIUrl":"https://doi.org/10.1016/s0165-6147(24)00130-5","url":null,"abstract":"No Abstract","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":"67 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549571","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 : 2024-07-05 DOI: 10.1016/s0165-6147(24)00126-3
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/s0165-6147(24)00126-3","DOIUrl":"https://doi.org/10.1016/s0165-6147(24)00126-3","url":null,"abstract":"No Abstract","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":"15 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141552892","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
Implications of innate immune sexual dimorphism for MASLD pathogenesis and treatment. 先天免疫性双态性对 MASLD 发病机制和治疗的影响。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-07-01 Epub Date: 2024-06-08 DOI: 10.1016/j.tips.2024.05.004
Richell Booijink, Prakash Ramachandran, Ruchi Bansal
{"title":"Implications of innate immune sexual dimorphism for MASLD pathogenesis and treatment.","authors":"Richell Booijink, Prakash Ramachandran, Ruchi Bansal","doi":"10.1016/j.tips.2024.05.004","DOIUrl":"10.1016/j.tips.2024.05.004","url":null,"abstract":"<p><p>Growing evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) is significantly higher in men versus women. Increased prevalence is observed in postmenopausal women, suggesting that age and sex (hormones) influence MASLD development and progression. Molecular data further reveal that sex regulates the innate immune responses with an essential role in MASLD progression. To date, there has been limited focus on the role of innate immune sexual dimorphism in MASLD, and differences between men and women are not considered in the current drug discovery landscape. In this review, we summarize the sex disparities and innate immune sexual dimorphism in MASLD pathogenesis. We further highlight the importance of harnessing sexual dimorphism in identifying therapeutic targets, developing pharmacological therapies, and designing (pre-) clinical studies for the personalized treatment for MASLD.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"614-627"},"PeriodicalIF":13.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296745","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
Targeting extranuclear histones to alleviate acute and chronic inflammation. 针对核外组蛋白缓解急性和慢性炎症。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-07-01 Epub Date: 2024-06-08 DOI: 10.1016/j.tips.2024.05.008
Gerry A F Nicolaes, Oliver Soehnlein
{"title":"Targeting extranuclear histones to alleviate acute and chronic inflammation.","authors":"Gerry A F Nicolaes, Oliver Soehnlein","doi":"10.1016/j.tips.2024.05.008","DOIUrl":"10.1016/j.tips.2024.05.008","url":null,"abstract":"<p><p>Extracellular histones instigate an inflammatory triad - centered on cytotoxicity, immune cell stimulation, and coagulation - ultimately shaping the dynamics and outcome of various inflammatory pathologies. Given the virtual absence of beneficial functions of histones in the extracellular space, in recent years a number of interference strategies have emerged. In this review we summarize pathogenic functions of extracellular histones and highlight current developments of therapeutic interference. Finally, we elaborate on the current status of preclinical attempts to interfere with extracellular histones in the context of a focus on sepsis and cardiovascular diseases, both of which are leading causes of mortality worldwide.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"651-662"},"PeriodicalIF":13.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296760","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
Peptide libraries: from epitope mapping to in-depth high-throughput analysis. 多肽文库：从表位图谱到深入的高通量分析。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-07-01 Epub Date: 2024-05-08 DOI: 10.1016/j.tips.2024.04.004
Debora Iaculli, Steven Ballet
{"title":"Peptide libraries: from epitope mapping to in-depth high-throughput analysis.","authors":"Debora Iaculli, Steven Ballet","doi":"10.1016/j.tips.2024.04.004","DOIUrl":"10.1016/j.tips.2024.04.004","url":null,"abstract":"<p><p>Peptide arrays are a valuable instrument in the characterization of protein-protein interactions (PPIs) and immunogenic regions. New methods were developed to exploit the high-throughput potential of peptide arrays to obtain more in-depth information, replacing traditional resource-intensive experiments. Here, we discuss the recent advances in peptide-array-based technologies and the remaining challenges.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"579-582"},"PeriodicalIF":13.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899573","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
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":" ","pages":"639-650"},"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":" ","pages":"628-638"},"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
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