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Trends in pharmacological sciences最新文献

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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
Reprogramming pain signaling through photopharmacology. 通过光药理学重新编程疼痛信号。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-01 Epub Date: 2026-08-15 DOI: 10.1016/j.tips.2026.07.005
Xinyi Fang, Cunyu Lin, Marc López-Cano, Qianming Chen, Francisco Ciruela, Jiu Lin
{"title":"Reprogramming pain signaling through photopharmacology.","authors":"Xinyi Fang, Cunyu Lin, Marc López-Cano, Qianming Chen, Francisco Ciruela, Jiu Lin","doi":"10.1016/j.tips.2026.07.005","DOIUrl":"10.1016/j.tips.2026.07.005","url":null,"abstract":"<p><p>Pain remains a major clinical challenge because current analgesics lack spatiotemporal precision and frequently induce systemic adverse effects, tolerance, and dependence. Recent advances in photopharmacology have enabled reversible optical control of ion channels, G protein-coupled receptors, and neural circuits involved in nociceptive processing, providing new opportunities for precision analgesia. Progress in photoswitches, photocaged ligands, wireless optoelectronic systems, and nanodelivery platforms has substantially improved the in vivo applicability of light-responsive therapeutics. These developments have transformed photopharmacology from a mechanistic research tool into a potential translational strategy for pain treatment. In this review, we discuss how photopharmacological approaches are reshaping the investigation of peripheral and central pain signaling, highlight emerging light-controlled analgesics, and outline future directions toward clinically translatable, nonaddictive, and personalized pain therapeutics.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"995-1007"},"PeriodicalIF":24.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761022","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
Trojan mast cells: repurposing allergy for targeted oncolytic delivery. 特洛伊肥大细胞：重新利用过敏靶向溶瘤传递。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-01 Epub Date: 2026-08-18 DOI: 10.1016/j.tips.2026.08.001
Mengqin Guo, Wenhao Wang, Zhengwei Huang
{"title":"Trojan mast cells: repurposing allergy for targeted oncolytic delivery.","authors":"Mengqin Guo, Wenhao Wang, Zhengwei Huang","doi":"10.1016/j.tips.2026.08.001","DOIUrl":"10.1016/j.tips.2026.08.001","url":null,"abstract":"<p><p>Oncolytic viruses hold immense therapeutic promise but face formidable systemic delivery barriers. A new study by Xu et al. engineered immunoglobulin E-sensitized mast cells to selectively ferry these viruses into tumors. Excitingly, antigen-triggered degranulation precisely releases the viral payload and reshapes the immune microenvironment, offering a highly modular delivery paradigm.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"949-951"},"PeriodicalIF":24.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798357","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
Lysosome-targeted protein degradation platforms for spatiotemporally controlled degradation. 时空可控降解的溶酶体靶向蛋白降解平台。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-01 Epub Date: 2026-08-14 DOI: 10.1016/j.tips.2026.07.007
Liheng Liang, Teng Zhang, Xingzhen Zhang, Lei Ye, Guangxi Zhai, Xiaoye Yang
{"title":"Lysosome-targeted protein degradation platforms for spatiotemporally controlled degradation.","authors":"Liheng Liang, Teng Zhang, Xingzhen Zhang, Lei Ye, Guangxi Zhai, Xiaoye Yang","doi":"10.1016/j.tips.2026.07.007","DOIUrl":"10.1016/j.tips.2026.07.007","url":null,"abstract":"<p><p>Lysosome-targeted protein degradation (LTPD) represents a therapeutic strategy that degrades membrane and extracellular target proteins through the endolysosomal pathway. LTPD chimeras are molecular degraders that mediate LTPD, but their in vivo performance is limited by poor spatiotemporal control of degradation-existing chimeras have suboptimal pharmacokinetics, tissue selectivity, and endolysosomal trafficking. To overcome these hurdles associated with chimeras, LTPD platforms have emerged. LTPD platforms function as chimera-loaded systems for targeted delivery and controlled release of chimeras, or as platform-based degraders that mediate disease-targeted and on-demand degradation without chimeras. We discuss how LTPD platforms spatiotemporally control degradation and describe their therapeutic applications. In particular, we summarize the design principles of LTPD platforms to address the stringent requirements imposed by the LTPD process. These principles may contribute to the rational design of LTPD platforms.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1035-1052"},"PeriodicalIF":24.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762159","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
Therapeutic antibodies targeting G protein-coupled receptors. 靶向G蛋白偶联受体的治疗性抗体。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-01 Epub Date: 2026-01-07 DOI: 10.1016/j.tips.2025.12.004
Qingyuan Xu, Keke Huang, Yibing Shi, Yuanlin Song, Tianlei Ying, Zhenlin Yang
{"title":"Therapeutic antibodies targeting G protein-coupled receptors.","authors":"Qingyuan Xu, Keke Huang, Yibing Shi, Yuanlin Song, Tianlei Ying, Zhenlin Yang","doi":"10.1016/j.tips.2025.12.004","DOIUrl":"10.1016/j.tips.2025.12.004","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are involved in numerous physiological and pathological processes. Therapeutic antibodies targeting GPCRs, including monoclonal antibodies (mAbs), single-domain antibodies (sdAbs), and antibody-drug conjugates (ADCs), represent a promising class of biologics with high specificity and therapeutic potential. The integration of innovative screening technologies, structural biology, and computational approaches has significantly accelerated the discovery of antibody-based therapeutics against GPCRs. In this review, we discuss the emerging strategies used in the development of these therapeutic antibodies, examine key insights from pathogenic autoantibodies, evaluate the clinical trial landscape, and explore how emerging technologies such as artificial intelligence (AI)-assisted design and membrane-mimetic systems are driving the next generation of GPCR-targeted therapeutics.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1021-1034"},"PeriodicalIF":24.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935062","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
Amyloidogenic amylin signaling links diabetes to dementia pathogenesis. 淀粉样蛋白原淀粉酶信号将糖尿病与痴呆发病机制联系起来。
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.2026.07.009
Florin Despa, Tammaryn Lashley
{"title":"Amyloidogenic amylin signaling links diabetes to dementia pathogenesis.","authors":"Florin Despa, Tammaryn Lashley","doi":"10.1016/j.tips.2026.07.009","DOIUrl":"10.1016/j.tips.2026.07.009","url":null,"abstract":"<p><p>Recent studies identify amyloidogenic human amylin, secreted by the pancreas, as a potential link between type-2 diabetes and Alzheimer's disease. Evidence suggests that pathogenic amylin signaling impairs cerebral bioenergetics, promoting tau hyperphosphorylation and neurodegeneration. Selective targeting of circulating amyloidogenic amylin and its pathogenic signaling may enable biomarker development and disease-modifying therapies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"955-958"},"PeriodicalIF":24.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707798","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
Recent advances in venom pharmacology reshaping venom-to-drug discovery. 毒液药理学的最新进展重塑了毒液对药物的发现。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-07-07 DOI: 10.1016/j.tips.2026.06.006
Tarek Mohamed Abd El-Aziz, Michel De Waard, Brij B Singh
{"title":"Recent advances in venom pharmacology reshaping venom-to-drug discovery.","authors":"Tarek Mohamed Abd El-Aziz, Michel De Waard, Brij B Singh","doi":"10.1016/j.tips.2026.06.006","DOIUrl":"10.1016/j.tips.2026.06.006","url":null,"abstract":"<p><p>Animal venoms represent rich sources of pharmacologically active molecules, yet their translation into clinical therapeutics has historically progressed slowly. Recent advances in AI-driven venomics, cryo-electron microscopy, and computational peptide engineering are helping to overcome long-standing barriers in venom-based drug discovery and accelerate therapeutic translation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"835-839"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405742","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
Orforglipron (Foundayo) for adults with obesity. Orforglipron （Foundayo）用于成人肥胖。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-07-08 DOI: 10.1016/j.tips.2026.06.007
Qingtong Zhou, Guanyi Li, Ming-Wei Wang
{"title":"Orforglipron (Foundayo) for adults with obesity.","authors":"Qingtong Zhou, Guanyi Li, Ming-Wei Wang","doi":"10.1016/j.tips.2026.06.007","DOIUrl":"10.1016/j.tips.2026.06.007","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"938-939"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412693","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
Surface-targeted complement modulation at biomedical interfaces. 生物医学界面表面靶向补体调节。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-07-11 DOI: 10.1016/j.tips.2026.06.005
Ekaterina Umnyakova, Jannes Felsch, Daniel Ricklin
{"title":"Surface-targeted complement modulation at biomedical interfaces.","authors":"Ekaterina Umnyakova, Jannes Felsch, Daniel Ricklin","doi":"10.1016/j.tips.2026.06.005","DOIUrl":"10.1016/j.tips.2026.06.005","url":null,"abstract":"<p><p>The complement system is essential for distinguishing self-tissue from foreign threats; however, complement activation on biomedical surfaces such as implants, transplants, or drug-delivery systems may lead to severe thromboinflammatory complications. Unlike systemic complement inhibitors, surface-targeted strategies remain scarce, despite their potential advantages regarding safety and efficacy. Recent years have seen the emergence of diverse surface-targeting approaches that impair different mechanisms underlying complement-mediated complications. These strategies, ranging from surface coatings to inhibitors targeting complement-tagged surfaces, are progressing from conceptual development to clinical application. In this review, we provide a comprehensive overview of complement-activation mechanisms on biomedical surfaces, highlight ongoing clinical investigations, and discuss a broad spectrum of emerging approaches to prevent adverse complement activation on biomedical interfaces.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"890-905"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424377","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
Forever chemicals, the microbiome, and brain health: towards therapeutics. 化学物质、微生物群和大脑健康：走向治疗学。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-08-01 Epub Date: 2026-07-24 DOI: 10.1016/j.tips.2026.06.010
Dhirendra Pratap Singh, Eileen Ryan, Gerard Clarke, John F Cryan
{"title":"Forever chemicals, the microbiome, and brain health: towards therapeutics.","authors":"Dhirendra Pratap Singh, Eileen Ryan, Gerard Clarke, John F Cryan","doi":"10.1016/j.tips.2026.06.010","DOIUrl":"10.1016/j.tips.2026.06.010","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are persistent xenobiotics linked to neurodevelopmental, neurodegenerative, and neurological disorders. PFAS-induced gut microbiota remodelling may disrupt gut-brain signalling, thereby affecting brain functions and behaviour. Integrating microbiome endpoints (diversity, taxonomic shifts, and metabolic configuration) into PFAS research provides a framework to elucidate toxicodynamic mechanisms and to inform the development of targeted, mechanism-based therapeutic strategies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"826-830"},"PeriodicalIF":24.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585241","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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