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VDAC2 brake release: unleashing inflammation via IFNγ. VDAC2刹车释放：通过IFNγ释放炎症。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-07-29 DOI: 10.1016/j.tips.2025.07.001
Swapneel J Patel, Zhijian J Chen
{"title":"VDAC2 brake release: unleashing inflammation via IFNγ.","authors":"Swapneel J Patel, Zhijian J Chen","doi":"10.1016/j.tips.2025.07.001","DOIUrl":"10.1016/j.tips.2025.07.001","url":null,"abstract":"<p><p>Identification of therapeutic vulnerabilities in cancer remains a high priority for cancer research. A recent CRISPR/Cas9 screen identified that VDAC2 deletion in tumors enhanced their sensitivity to interferon-γ (IFNγ) through the release of mitochondrial DNA (mtDNA) and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. These data suggest that VDAC2 inhibition could enhance antitumor therapies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"695-696"},"PeriodicalIF":19.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754388","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
Shining light on parvalbumin interneuron plasticity. 照亮小白蛋白中间神经元的可塑性。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-07-05 DOI: 10.1016/j.tips.2025.06.006
Marina P Hommersom, Dirk Schubert, Nael Nadif Kasri
{"title":"Shining light on parvalbumin interneuron plasticity.","authors":"Marina P Hommersom, Dirk Schubert, Nael Nadif Kasri","doi":"10.1016/j.tips.2025.06.006","DOIUrl":"10.1016/j.tips.2025.06.006","url":null,"abstract":"<p><p>Neuronal networks rely on a balance between the activity of excitatory and inhibitory neurons, each having distinct roles in regulating the flow of activity across brain circuits and signal processing. Recent work by Selten et al. uncovers how parvalbumin (PV)-expressing interneurons adjust their inhibitory inputs in response to activity changes, revealing a neuropeptide-based mechanism.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"697-699"},"PeriodicalIF":19.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576337","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
Piezo1: structural pharmacology and mechanotransduction mechanisms. Piezo1：结构药理学和机械转导机制。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-07-31 DOI: 10.1016/j.tips.2025.06.009
Junyu Wang, Fangyuan Jing, Yinuo Zhao, Zilong You, Anren Zhang, Shugang Qin
{"title":"Piezo1: structural pharmacology and mechanotransduction mechanisms.","authors":"Junyu Wang, Fangyuan Jing, Yinuo Zhao, Zilong You, Anren Zhang, Shugang Qin","doi":"10.1016/j.tips.2025.06.009","DOIUrl":"10.1016/j.tips.2025.06.009","url":null,"abstract":"<p><p>Piezo1, a mechanosensitive ion channel protein, is a highly promising target for drug development. We systematically review the latest advances in its structural features, signal transduction mechanisms, and functional roles in various pathological processes including neurological diseases, cardiovascular diseases, and cancer. Furthermore, we provide an in-depth analysis of three key challenges in developing Piezo1-targeted drugs, including the complexity of its dynamic structure and regulatory network, the difficulty of achieving specific targeting, and the off-target risks and potential systemic toxicity arising from its widespread physiological functions. Finally, we highlight that integrating cutting-edge technologies, such as super-resolution imaging, artificial intelligence (AI)-assisted drug design, and organoid/organ-on-a-chip models, holds great promise for overcoming these challenges and accelerating the development and clinical translation of Piezo1-targeted drugs.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"752-770"},"PeriodicalIF":19.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765581","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 plasma membrane cholesterol as a novel anticancer therapy. 靶向质膜胆固醇作为一种新的抗癌疗法。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-06-19 DOI: 10.1016/j.tips.2025.06.001
Alfredo Erazo-Oliveras, Mónica Muñoz-Vega, Robert S Chapkin
{"title":"Targeting plasma membrane cholesterol as a novel anticancer therapy.","authors":"Alfredo Erazo-Oliveras, Mónica Muñoz-Vega, Robert S Chapkin","doi":"10.1016/j.tips.2025.06.001","DOIUrl":"10.1016/j.tips.2025.06.001","url":null,"abstract":"<p><p>An effective therapeutic strategy to treat oncogenic Wnt signaling in the context of colorectal cancer (CRC) remains elusive. A new study from Cho and colleagues describes a novel mechanistic link between the loss of canonical adenomatous polyposis coli (APC) function, membrane cholesterol, and an innovative drug target to specifically suppress the cholesterol-Dvl-β-catenin signaling axis.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"700-702"},"PeriodicalIF":19.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337036","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
Ion channels as therapeutic targets in osteoarthritis. 离子通道作为骨关节炎的治疗靶点。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-07-10 DOI: 10.1016/j.tips.2025.06.003
Renpeng Zhou, Wei Hu, Stephen G Waxman, Chuan-Ju Liu
{"title":"Ion channels as therapeutic targets in osteoarthritis.","authors":"Renpeng Zhou, Wei Hu, Stephen G Waxman, Chuan-Ju Liu","doi":"10.1016/j.tips.2025.06.003","DOIUrl":"10.1016/j.tips.2025.06.003","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a leading cause of disability worldwide and is characterized by cartilage loss, inflammation, and pain. Despite advances, effective disease-modifying treatments are lacking. Emerging evidence highlights ion channels as key regulators of OA that affect chondrocyte survival, mechanotransduction, inflammation, and nociception. This review discusses ion channel families - including sodium, potassium, TRP, Piezo, acid-sensing, and chloride channels, as well as ligand-gated receptors - and their roles in OA progression. We explore preclinical and clinical advances in ion channel-targeted therapies, such as small-molecule inhibitors, biologics, and gene therapies, as well as repurposing of existing drugs for symptom relief and disease modification. Challenges in selective targeting, pharmacological and drug delivery strategies, and patient stratification are also addressed. Continued research on ion channel biology is essential for developing targeted OA therapies to enable precision medicine via site-specific strategies that minimize systemic side effects.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"792-813"},"PeriodicalIF":19.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620731","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
PSA inhibitors for contraception: insights from prostate cancer. PSA抑制剂用于避孕：来自前列腺癌的见解。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-07-01 Epub Date: 2025-06-04 DOI: 10.1016/j.tips.2025.05.005
Wipawee Winuthayanon
{"title":"PSA inhibitors for contraception: insights from prostate cancer.","authors":"Wipawee Winuthayanon","doi":"10.1016/j.tips.2025.05.005","DOIUrl":"10.1016/j.tips.2025.05.005","url":null,"abstract":"<p><p>Despite the availability of effective hormonal contraceptive methods, nearly half of pregnancies worldwide remain unintended, highlighting the urgent need for innovative, nonhormonal options. Prostate-specific antigen (PSA) is a biomarker for prostate cancer and is well established for its role in liquefying semen by hydrolyzing gel-forming proteins. Liquefaction is essential for sperm motility and fertilization, making PSA inhibition a prime candidate for novel contraceptive strategies. Advances in prostate cancer research have led to the development of PSA inhibitors for cancer therapeutic purposes, including drugs that suppress PSA activity or selectively kill PSA-expressing cells. PSA presents a unique target as it is produced in men and acts in women, making it a promising contraceptive strategy for both sexes. This opinion explores the potential adaptation of existing PSA inhibitors from the oncology field for contraceptive applications. It also highlights emerging strategies to identify effective PSA-targeted contraceptive candidates, opening new avenues for next-generation nonhormonal contraception for men and women.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"599-609"},"PeriodicalIF":19.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235331","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 approaches for antagonizing the aryl hydrocarbon receptor. 拮抗芳烃受体的新方法。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-07-01 Epub Date: 2025-06-05 DOI: 10.1016/j.tips.2025.05.003
Zdeněk Dvořák, Sridhar Mani, Jan Vondráček
{"title":"Emerging approaches for antagonizing the aryl hydrocarbon receptor.","authors":"Zdeněk Dvořák, Sridhar Mani, Jan Vondráček","doi":"10.1016/j.tips.2025.05.003","DOIUrl":"10.1016/j.tips.2025.05.003","url":null,"abstract":"<p><p>Antagonizing the aryl hydrocarbon receptor (AhR) is a highly pertinent pharmacotherapeutic strategy. To overcome the drawbacks of existing AhR antagonists, novel molecules that can selectively target canonical and noncanonical AhR pathways are urgently needed. Recent reports on the structures and functions of cytosolic and nuclear AhR-protein complexes have allowed for understanding structural determinants for intrinsic activity and functional selectivity of AhR ligands. This new information regarding AhR surface interactions has opened new avenues for the development of novel AhR antagonists. Achievable strategies include the negative allosteric modulation of AhR and the disruption of AhR-protein and AhR-DNA interfaces using peptidomimetics or small molecules. Here, we discuss such novel approaches that may lead to new AhR-targeted therapeutics.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"629-637"},"PeriodicalIF":19.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249713","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
Protein acylations in cancer immunity: effects and therapeutic opportunities. 蛋白质酰化在癌症免疫中的作用和治疗机会。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-07-01 Epub Date: 2025-06-20 DOI: 10.1016/j.tips.2025.05.011
Jia-Cheng Lai, Yi-Ting Jiang, Shougeng Liu, Simeng Wang, Wei Cui, Lihui Wang
{"title":"Protein acylations in cancer immunity: effects and therapeutic opportunities.","authors":"Jia-Cheng Lai, Yi-Ting Jiang, Shougeng Liu, Simeng Wang, Wei Cui, Lihui Wang","doi":"10.1016/j.tips.2025.05.011","DOIUrl":"10.1016/j.tips.2025.05.011","url":null,"abstract":"<p><p>Acylations are conserved and dynamic modifications that control various biological processes, including gene transcription and protein biology, and have been tied to diseases, such as cancers. Due to their reversible characteristic, acylations exhibit great therapeutic potential through targeting of their regulatory enzymes and proteins. Recent studies have improved our understanding of the close interplay between acylations and the tumor immune microenvironment (TIME), showing the potential to improve antitumor immune responses via acylation manipulation. Herein, we review the effects of acylations, including acetylation, lactylation, palmitoylation, and some less well-known acylations on cancer immunity, and corresponding therapeutic opportunities. Specifically, we bring into focus diverse roles of different acylation-related enzymes, metabolites, or substrates to provide insights into targeting acylations to increase antitumor immunity and generate broader research enthusiasm.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"653-673"},"PeriodicalIF":19.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337035","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
Bright sorting yields drug-like anti-amyloid antibodies. 明亮分选产生类似药物的抗淀粉样抗体。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-07-01 Epub Date: 2025-06-16 DOI: 10.1016/j.tips.2025.05.013
Bingqian Li, Pietro Sormanni
{"title":"Bright sorting yields drug-like anti-amyloid antibodies.","authors":"Bingqian Li, Pietro Sormanni","doi":"10.1016/j.tips.2025.05.013","DOIUrl":"10.1016/j.tips.2025.05.013","url":null,"abstract":"<p><p>Conformation-specific antibodies represent powerful tools for targeting pathogenic amyloid aggregates. However, the discovery of aggregate-selective antibodies with drug-like developability properties has been slow, inefficient, and difficult to generalise across different amyloid targets. The Tessier lab has developed a yeast-display screening pipeline that enables conformation-specific antibody discovery against diverse aggregated proteins.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"587-589"},"PeriodicalIF":19.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317968","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
Limiting TDP-43 aggregation by induced recruitment to PML-NB. 通过诱导募集PML-NB限制TDP-43聚集。
IF 19.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-07-01 Epub Date: 2025-06-05 DOI: 10.1016/j.tips.2025.05.012
Chien-Han Kao, Ruey-Hwa Chen
{"title":"Limiting TDP-43 aggregation by induced recruitment to PML-NB.","authors":"Chien-Han Kao, Ruey-Hwa Chen","doi":"10.1016/j.tips.2025.05.012","DOIUrl":"10.1016/j.tips.2025.05.012","url":null,"abstract":"<p><p>TAR DNA binding protein 43 kD (TDP-43) aggregation is associated with several neurodegenerative diseases and limiting TDP-43 aggregates could offer therapeutic benefit. Recently, Wagner et al. utilized the induced proximity to PML for enhancing TDP-43 solubility under stress. Mechanistically, this strategy triggers a SUMOylation-ubiquitylation cascade on TDP-43 and the compartmentalization of TDP-43 to the promyelocytic leukemia-nuclear bodies (PML-NBs).</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"593-595"},"PeriodicalIF":19.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249714","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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