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Targeting CH25H restores p62-mediated α-synuclein clearance. 靶向CH25H恢复p62介导的α-突触核蛋白清除。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-28 DOI: 10.1016/j.tips.2026.09.002
Gavin S Dawe
{"title":"Targeting CH25H restores p62-mediated α-synuclein clearance.","authors":"Gavin S Dawe","doi":"10.1016/j.tips.2026.09.002","DOIUrl":"https://doi.org/10.1016/j.tips.2026.09.002","url":null,"abstract":"<p><p>Astrocytes remove extracellular α-synuclein aggregates through p62-dependent autophagy, yet the factors limiting this defense remain unclear. Zhang and colleagues recently identified cholesterol 25-hydroxylase as an inducible negative regulator of p62-mediated clearance. Genetic suppression or a p62-derived decoy peptide reduced α-synuclein pathology in mouse models of Parkinson's disease.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075856","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
B cells enter the synaptic conversation. B细胞进入突触对话。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-23 DOI: 10.1016/j.tips.2026.09.004
Terry R Suk, David Gate
{"title":"B cells enter the synaptic conversation.","authors":"Terry R Suk, David Gate","doi":"10.1016/j.tips.2026.09.004","DOIUrl":"10.1016/j.tips.2026.09.004","url":null,"abstract":"<p><p>Synapse loss is a defining feature of neurodegenerative disease, yet the signals that orchestrate synaptic elimination remain incompletely understood. Crowley and colleagues uncover an unexpected link between neuronal hyperactivity and adaptive immunity, showing that antibody-secreting B cells and immunoglobulins can drive complement-dependent synapse loss.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031190","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 emerging landscape for next-generation HNSCC treatment. 下一代HNSCC治疗的新兴前景。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-22 DOI: 10.1016/j.tips.2026.09.007
Kailey N Jackett, Meghri Katerji, Kiranya Arnold, Kyunghee Burkitt, Andrew Gennaro, Vassiliki Saloura, John Brognard
{"title":"The emerging landscape for next-generation HNSCC treatment.","authors":"Kailey N Jackett, Meghri Katerji, Kiranya Arnold, Kyunghee Burkitt, Andrew Gennaro, Vassiliki Saloura, John Brognard","doi":"10.1016/j.tips.2026.09.007","DOIUrl":"10.1016/j.tips.2026.09.007","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is a biologically complex malignancy in which durable responses to standard multimodal therapies, targeted therapies, and immune checkpoint inhibitors remain limited. Therapeutic resistance arises from interconnected oncogenic signaling, tumor plasticity, heterogeneity, and immune evasion, which enable tumors to bypass inhibition of individual pathways. These mechanisms also differ across biologically distinct HNSCC subsets, including human papillomavirus (HPV)-positive and HPV-negative disease. Emerging therapeutic platforms in preclinical and clinical development, including targeted protein degraders, engineered antibodies, cellular and vaccine-based immunotherapies, photoimmunotherapy, and epigenetic modulators, provide new opportunities to target these interconnected vulnerabilities. In this review, we examine how these pharmacological strategies may overcome resistance in HNSCC and discuss their integration into biomarker-guided, mechanism-driven combination regimens.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13693649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138487","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
Closing AI drug-regulatory gaps through harmonized oversight. 通过协调监督缩小人工智能药物监管差距。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-16 DOI: 10.1016/j.tips.2026.09.001
Surendra Sarsaiya, Archana Jain, Jishuang Chen, Qihai Gong
{"title":"Closing AI drug-regulatory gaps through harmonized oversight.","authors":"Surendra Sarsaiya, Archana Jain, Jishuang Chen, Qihai Gong","doi":"10.1016/j.tips.2026.09.001","DOIUrl":"https://doi.org/10.1016/j.tips.2026.09.001","url":null,"abstract":"<p><p>Artificial intelligence (AI) not only accelerates drug discovery but also creates regulatory gaps-with more than 100 AI-assisted pipelines in trials. Frameworks lack enforceable standards. We propose a risk-tiered framework that distinguishes discovery AI from evidence-generating AI, mandates impact assessments and Investigational New Drug disclosure when AI influences decisions, and transforms guidelines into binding, risk-proportionate regulation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983628","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
October 2026 issue first authors. 2026年10月号第一作者。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-16 DOI: 10.1016/j.tips.2026.08.016
Yang Zhou, Shihang Wang, Nicholas McKee, Yuwei Tang, Yang Xu, Sebastián A Suarez
{"title":"October 2026 issue first authors.","authors":"Yang Zhou, Shihang Wang, Nicholas McKee, Yuwei Tang, Yang Xu, Sebastián A Suarez","doi":"10.1016/j.tips.2026.08.016","DOIUrl":"https://doi.org/10.1016/j.tips.2026.08.016","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983705","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
STAT3 signaling inhibitors for cancer treatment. STAT3信号抑制剂用于癌症治疗。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-01 Epub Date: 2026-08-08 DOI: 10.1016/j.tips.2026.07.004
Rasaq Akinsola, Jing Xian, James Turkson
{"title":"STAT3 signaling inhibitors for cancer treatment.","authors":"Rasaq Akinsola, Jing Xian, James Turkson","doi":"10.1016/j.tips.2026.07.004","DOIUrl":"10.1016/j.tips.2026.07.004","url":null,"abstract":"<p><p>Pharmacological targeting of Signal Transducer and Activator of Transcription 3 (STAT3) in cancer has demonstrable antitumor efficacy. However, suitably potent, efficacious, and safe STAT3 inhibitors are scarce, and only a handful have entered clinical trials, limiting our knowledge of the extent of clinical benefit. Outcomes of recently completed trials in advanced cancers range from improved overall survival and complete responses in a cohort of patients with phosphotyrosine STAT3 positivity to partial responses and progressive disease in unselected patients. Advancements in oligonucleotide technologies and the integration of E3 ligase-specific proteolysis-targeting chimeras and molecular glue protein degrader strategies are accelerating the transition of STAT3 inhibitors into clinical testing. This review examines recent STAT3-targeted modalities and their preclinical and clinical activities. It concludes by underscoring the value of biomarker-informed approaches to optimize patient outcomes, combination therapies to improve clinical benefits, and artificial intelligence/machine learning tools to accelerate development.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"959-978"},"PeriodicalIF":24.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697925","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
Sex-sensitive serotonergic signaling in psychedelic pharmacology. 致幻剂药理学中性别敏感的血清素能信号。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-01 Epub Date: 2026-08-10 DOI: 10.1016/j.tips.2026.07.006
Sofia Nasini, Benedetta Barzon, Antonino Casile, Brandon Richardson, Gabriella Gobbi, Stefano Comai
{"title":"Sex-sensitive serotonergic signaling in psychedelic pharmacology.","authors":"Sofia Nasini, Benedetta Barzon, Antonino Casile, Brandon Richardson, Gabriella Gobbi, Stefano Comai","doi":"10.1016/j.tips.2026.07.006","DOIUrl":"10.1016/j.tips.2026.07.006","url":null,"abstract":"<p><p>Classic serotonergic psychedelics act primarily via 5-HT2A receptor agonism, yet their therapeutic effects and biological responses are heterogeneous. Biological sex remains an underexamined source of this variability because many clinical and preclinical studies have not been designed to test sex-by-treatment effects. Recent preclinical findings, together with more limited human evidence, suggest that sex and endocrine state can modulate serotonergic mechanisms relevant to psychedelic action, including 5-HT1A autoregulatory feedback, 5-HT2A signaling, serotonin clearance, neuroendocrine coupling, and neuroplastic cascades. This review synthesizes how sex- and state-sensitive serotonergic regulation may influence psychedelic signaling and outlines priorities for sex-informed translational research in preclinical and clinical settings.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1008-1020"},"PeriodicalIF":24.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707781","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
Elamipretide: a mitochondria-targeting drug for Barth syndrome. Elamipretide：一种线粒体靶向治疗Barth综合征的药物。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-01 Epub Date: 2026-07-14 DOI: 10.1016/j.tips.2026.06.011
Andrea Villatore, Emily A Ehle, Stephen P Chelko
{"title":"Elamipretide: a mitochondria-targeting drug for Barth syndrome.","authors":"Andrea Villatore, Emily A Ehle, Stephen P Chelko","doi":"10.1016/j.tips.2026.06.011","DOIUrl":"10.1016/j.tips.2026.06.011","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1053-1054"},"PeriodicalIF":24.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148449551","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
Sequential EGFR inhibition sensitizes glioblastoma to temozolomide. 序贯EGFR抑制使胶质母细胞瘤对替莫唑胺敏感。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-01 Epub Date: 2026-08-17 DOI: 10.1016/j.tips.2026.07.010
Xiaozhou Yu, Runxin Wu, Shi-Yuan Cheng
{"title":"Sequential EGFR inhibition sensitizes glioblastoma to temozolomide.","authors":"Xiaozhou Yu, Runxin Wu, Shi-Yuan Cheng","doi":"10.1016/j.tips.2026.07.010","DOIUrl":"10.1016/j.tips.2026.07.010","url":null,"abstract":"<p><p>Glioblastoma (GBM) remains a devastating disease for which standard temozolomide chemotherapy is limited by O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT)-mediated DNA damage repair. By targeting epidermal growth factor receptor (EGFR), a major oncogenic driver of GBM, Guo, Habib, and colleagues demonstrate that EGFR inhibition prior to temozolomide treatment induces an adaptive response that downregulates MGMT, enhancing therapeutic efficacy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"952-954"},"PeriodicalIF":24.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798336","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
Tau-targeting pharmacological strategies in neurodegenerative disease. 神经退行性疾病中tau靶向药物策略。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-01 Epub Date: 2026-08-17 DOI: 10.1016/j.tips.2026.07.008
Hanyuan Zheng, Jie Zheng
{"title":"Tau-targeting pharmacological strategies in neurodegenerative disease.","authors":"Hanyuan Zheng, Jie Zheng","doi":"10.1016/j.tips.2026.07.008","DOIUrl":"10.1016/j.tips.2026.07.008","url":null,"abstract":"<p><p>Pathological tau accumulation underlies a spectrum of neurodegenerative diseases collectively known as tauopathies. Although reducing tau remains the prevailing therapeutic strategy, indiscriminate tau reduction may compromise physiological functions and has demonstrated limited clinical efficacy. Growing evidence indicates disease- and stage-specific tau heterogeneity-spanning post-translational modifications (PTMs), aggregation states, and vulnerable cell populations-highlighting the necessity for improved targeting selectivity for pathological tau species. In this review, we discuss tau-targeting therapeutic modalities, including nucleic acids to suppress tau expression, immunotherapies and chimeric degraders to facilitate tau protein clearance, inhibitors of aggregation, and emerging strategies for tau PTM-editing and cellular-level interventions for neurofibrillary tangle-bearing neurons.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"979-994"},"PeriodicalIF":24.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798388","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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