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Visceral obesity and HFpEF: targets and therapeutic opportunities.
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-03-19 DOI: 10.1016/j.tips.2025.02.005
Yilin Li, Zhuofeng Lin, Yulin Li
{"title":"Visceral obesity and HFpEF: targets and therapeutic opportunities.","authors":"Yilin Li, Zhuofeng Lin, Yulin Li","doi":"10.1016/j.tips.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.tips.2025.02.005","url":null,"abstract":"<p><p>The effectiveness of weight-loss drugs in heart failure (HF) with preserved ejection fraction (HFpEF) highlights the link between obesity (adipose tissue) and HF (the heart). Recent guidelines incorporating the waist:height ratio for diagnosing and treating obesity reflect the growing recognition of the significance of visceral adiposity. However, its unique impact on HFpEF and their complex relationship remain underexplored. With limited treatment options for obesity-related HFpEF, novel disease-modifying treatments are urgently needed. Here, we clarify the relationship between visceral obesity and HFpEF, introducing the concept of the visceral adipose tissue-heart axis to explore its mechanisms and therapeutic potential. We also discuss promising strategies targeting visceral obesity in HFpEF and propose directions for future research.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671011","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 autism and Fragile X syndrome treatments.
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-03-17 DOI: 10.1016/j.tips.2025.02.004
Michael Parkhill, Natalina Salmaso, Amedeo D'Angiulli, Vivian Lee, Argel Aguilar-Valles
{"title":"Emerging autism and Fragile X syndrome treatments.","authors":"Michael Parkhill, Natalina Salmaso, Amedeo D'Angiulli, Vivian Lee, Argel Aguilar-Valles","doi":"10.1016/j.tips.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.tips.2025.02.004","url":null,"abstract":"<p><p>The limitations of current symptom-focused treatments drive the urgent need for effective therapies for autism and Fragile X syndrome (FXS). Currently, no approved pharmacological interventions target the core symptoms of these disorders. Advances in understanding the underlying biology of autism and FXS make this an important time to explore novel options. Indeed, several treatments have recently been tested in clinical trials, with promising results in treating core symptoms of autism and FXS. We focus on emerging interventions, such as gut microbiome therapies, anti-inflammatory approaches, bumetanide, phosphodiesterase 4D inhibitors, and endocannabinoid modulators. We also discuss factors, such as disorder heterogeneity, which may have contributed to poor efficacy in previously failed late-phase trials and impact recent trials, emphasizing the need for personalized treatment approaches.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658645","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
HSV-1 as a gene delivery platform for cancer gene therapy.
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-03-10 DOI: 10.1016/j.tips.2025.02.006
Yangkun Shen, Hucheng Zhang, Mengzhou Xue, Chunfu Zheng, Qi Chen
{"title":"HSV-1 as a gene delivery platform for cancer gene therapy.","authors":"Yangkun Shen, Hucheng Zhang, Mengzhou Xue, Chunfu Zheng, Qi Chen","doi":"10.1016/j.tips.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.tips.2025.02.006","url":null,"abstract":"<p><p>Herpes simplex virus type 1 (HSV-1) is a DNA virus with strong replication capabilities, a large genomic payload (≥30 kb), and low toxicity, making it a prominent vector in cancer gene therapy. Clinically approved oncolytic HSV-1 (oHSV-1) variants, such as T-VEC and G47Δ, demonstrate safety and efficacy in localized tumors, but face challenges in treating metastatic disease. To address this issue, next-generation oHSV-1 designs focus on precision targeting and immune remodeling through the delivery of multiple exogenous genes. In this review, we provide an overview of the inherent characteristics of oHSV-1 as a gene delivery platform, focusing on its genetic modification strategies, safety challenges in clinical applications, and future directions to maximize its therapeutic potential.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606437","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
Pain Signaling by GPCRs and RTKs.
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-03-07 DOI: 10.1016/j.tips.2025.02.002
Brain L Schmidt, Francesco De Logu, Romina Nassini, Pierangelo Geppetti, Nigel W Bunnett
{"title":"Pain Signaling by GPCRs and RTKs.","authors":"Brain L Schmidt, Francesco De Logu, Romina Nassini, Pierangelo Geppetti, Nigel W Bunnett","doi":"10.1016/j.tips.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.tips.2025.02.002","url":null,"abstract":"<p><p>Chronic pain is common and debilitating, yet is inadequately treated by current therapies, which can have life-threatening side effects. Treatments targeting G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs), key pain mediators, often fail in clinical trials for unknown reasons. Here, we discuss the recent evidence that GPCRs and RTKs generate sustained signals from multiprotein signaling complexes or signalosomes in intracellular compartments to control chronic pain. We evaluate the evidence that selective antagonism of these intracellular signals provides more efficacious and long-lasting pain relief than antagonism of receptors at the surface of cells. We highlight how the identification of coreceptors and molecular scaffolds that underpin pain signaling by multiple receptors has identified new therapeutic targets for chronic pain, surmounting the redundancy of the pain signaling pathway.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587228","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
A mechanism for ligand-dependent activation of AHR.
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-03-07 DOI: 10.1016/j.tips.2025.02.007
Audrey Guesdon, William Bourguet
{"title":"A mechanism for ligand-dependent activation of AHR.","authors":"Audrey Guesdon, William Bourguet","doi":"10.1016/j.tips.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.tips.2025.02.007","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AHR) is a crucial chemosensory protein and an emerging therapeutic target. However, the lack of structural data has long hindered a complete understanding of the mechanisms driving its function. Recently, Wu and colleagues reported a structural analysis of various DNA-bound AHR-ligand complexes, suggesting a ligand-driven activation mechanism.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587226","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
Levacetylleucine (N-acetyl-l-leucine) for Niemann-Pick disease type C.
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-03-06 DOI: 10.1016/j.tips.2025.02.003
Raquel van Gool, Walla Al-Hertani, Olaf Bodamer, Jaymin Upadhyay
{"title":"Levacetylleucine (N-acetyl-l-leucine) for Niemann-Pick disease type C.","authors":"Raquel van Gool, Walla Al-Hertani, Olaf Bodamer, Jaymin Upadhyay","doi":"10.1016/j.tips.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.tips.2025.02.003","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587227","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
Ribosome-directed cancer therapies: the tip of the iceberg?
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-03-04 DOI: 10.1016/j.tips.2025.02.001
Gregory C Howard, William P Tansey
{"title":"Ribosome-directed cancer therapies: the tip of the iceberg?","authors":"Gregory C Howard, William P Tansey","doi":"10.1016/j.tips.2025.02.001","DOIUrl":"10.1016/j.tips.2025.02.001","url":null,"abstract":"<p><p>Ribosomes and ribosome biogenesis (RiBi) are universally corrupted in cancer, fueling the high rates of translation that sustain malignancy and creating opportunities for discriminating therapeutic intervention. Despite longstanding recognition of the promise of ribosome-directed cancer therapies, only a handful of such agents have been used in the clinic, and with limited success, and the true potential of this approach is unknown. In the past few years, however, understanding of cancer ribosome specialization and the intricacies of RiBi have advanced dramatically, opening opportunities that could not be imagined when existing agents were discovered. Here, we discuss the rationale for targeting ribosomes to treat cancer, review the limitations of current agents, and highlight an important set of recent discoveries we propose could be exploited to discover molecularly-targeted ribosome-directed cancer therapeutics.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568200","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
Poison exons: tuning RNA splicing for targeted gene regulation.
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-03-01 Epub Date: 2025-02-05 DOI: 10.1016/j.tips.2025.01.002
Christopher R Neil, Cassandra Schaening-Burgos, Maria S Alexis, Dominic J Reynolds, Peter G Smith, Michael W Seiler, Frédéric H Vaillancourt, Anant A Agrawal
{"title":"Poison exons: tuning RNA splicing for targeted gene regulation.","authors":"Christopher R Neil, Cassandra Schaening-Burgos, Maria S Alexis, Dominic J Reynolds, Peter G Smith, Michael W Seiler, Frédéric H Vaillancourt, Anant A Agrawal","doi":"10.1016/j.tips.2025.01.002","DOIUrl":"10.1016/j.tips.2025.01.002","url":null,"abstract":"<p><p>Poison exons (PEs) are a class of alternatively spliced exons whose inclusion targets mRNA transcripts for degradation via the nonsense-mediated decay (NMD) pathway. Although a role for NMD as an essential mRNA quality control pathway has long been appreciated, recent advances in RNA sequencing (RNA-seq) strategies and analyses have revealed that its coupling to RNA splicing is broadly used to regulate mRNA stability and abundance. Regulation of PE splicing affects patterns of targeted degradation across the transcriptome and influences gene expression in both healthy and disease states. Importantly, PEs represent a novel therapeutic opportunity to modulate the expression of disease-relevant genes with sequence-specific resolution. We review the emergence of PE splicing in endogenous gene regulation, its misregulation in disease, and the ways in which it can be leveraged for therapeutic benefit.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"264-278"},"PeriodicalIF":13.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366002","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
The N terminus-only function of adhesion GPCRs: emerging concepts.
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-03-01 Epub Date: 2025-02-15 DOI: 10.1016/j.tips.2025.01.004
Laura Lehmann, Victoria Elisabeth Groß, Rene Behlendorf, Simone Prömel
{"title":"The N terminus-only function of adhesion GPCRs: emerging concepts.","authors":"Laura Lehmann, Victoria Elisabeth Groß, Rene Behlendorf, Simone Prömel","doi":"10.1016/j.tips.2025.01.004","DOIUrl":"10.1016/j.tips.2025.01.004","url":null,"abstract":"<p><p>Adhesion G-protein-coupled receptors (aGPCRs) play key roles in health and disease. They are unique in that they not only activate G-protein pathways but also have distinct functions that rely solely on their N termini, making them complex drug targets. To date there have been only descriptive observations about these enigmatic N terminus-only functions. Emerging evidence from several aGPCRs now indicates that these are a defining characteristic of these receptors that allows them to operate bidirectionally across environments. Recent advances in characterizing aGPCR splice variants and receptor structure have revealed the G protein-independent mechanisms that underlie their N terminus-only functions. This review consolidates current findings, explores how the N termini integrate functions, and identifies common principles across aGPCRs. We consider the therapeutic implications and discuss how specifically targeting N terminus functions provides a novel perspective on the pharmacological potential of aGPCRs.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"231-248"},"PeriodicalIF":13.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426265","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
IRAK4: potential therapeutic target for airway disease exacerbations. IRAK4：气道疾病恶化的潜在治疗靶点
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-03-01 Epub Date: 2025-01-16 DOI: 10.1016/j.tips.2025.01.001
Joseph A Jude, Reynold A Panettieri
{"title":"IRAK4: potential therapeutic target for airway disease exacerbations.","authors":"Joseph A Jude, Reynold A Panettieri","doi":"10.1016/j.tips.2025.01.001","DOIUrl":"10.1016/j.tips.2025.01.001","url":null,"abstract":"<p><p>Inflammatory lung diseases represent a significant healthcare burden. There is an unmet need for identifying therapeutic targets for inflammatory lung diseases, such as asthma, and chronic obstructive pulmonary disease (COPD). In a recent study, Sayers et al. validate the inhibition of interleukin (IL)-1 receptor-associated kinase (IRAK)-4 as a potential therapeutic strategy toward lung inflammation and inflammatory airway diseases more generally.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"201-203"},"PeriodicalIF":13.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012266","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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