Pharmacological Reviews最新文献

{"title":"Targeting of kinases to treat neurodegenerative diseases.","authors":"Tara Shomali, Jean-François Trempe","doi":"10.1016/j.pharmr.2026.100128","DOIUrl":"https://doi.org/10.1016/j.pharmr.2026.100128","url":null,"abstract":"<p><p>Neurodegenerative diseases, including Alzheimer, Parkinson, and multiple sclerosis, represent a growing global health crisis with limited therapeutic options that address disease progression. Protein kinases, which are crucial regulators of diverse cellular processes such as endolysosomal trafficking, neuroinflammation, and mitochondrial homeostasis, are frequently dysregulated in these conditions, making them attractive drug targets. This review explores the therapeutic potential of targeting key kinases implicated in neurodegeneration, specifically p38 MAPK, BTK, c-Abl/ABL1, CDK5, GSK3, JNK, LRRK2, and PINK1. We delve into their specific roles in disease pathophysiology, current therapeutic strategies, and the structural insights guiding our understanding of these kinases and the development of more selective inhibitors. Although significant challenges remain, particularly regarding selectivity and drug delivery to the brain, the advancements in our understanding of kinase biology and novel therapeutic modalities offer substantial promise for developing disease-modifying treatments. This review highlights the urgent need for continued research to identify new targets and translate these scientific breakthroughs into effective therapies for patients. SIGNIFICANCE STATEMENT: This review outlines the roles of protein kinases in neurodegenerative diseases and highlights emerging strategies for their therapeutic modulation. By integrating current knowledge of kinase signaling, drug development, and pharmacokinetics, this work provides a timely and practical framework to guide the development of disease-modifying treatments in an area of pressing clinical need.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 3","pages":"100128"},"PeriodicalIF":17.3,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513964","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}

{"title":"Reimagining pharmacology education.","authors":"Clare Guilding, Roisin Kelly-Laubscher, Margaret Cunningham, Tinne Dilles, David Kennedy, David J Brinkman, Ali H Eid, Kelly M Quesnelle, Ferdi Engels, Simon Maxwell, Arthur Christopoulos, Paul J White","doi":"10.1016/j.pharmr.2026.100126","DOIUrl":"https://doi.org/10.1016/j.pharmr.2026.100126","url":null,"abstract":"<p><p>We are arguably experiencing the greatest disruption to higher education in modern history. High-quality education research has demonstrated that active learning and other innovations are significantly more effective than traditional methods. The recent pandemic forced educators to adapt in previously unimaginable ways. Generative artificial intelligence now presents great challenges and opportunities for our approaches to teaching, support of learning and assessment, such as streamlining personalized feedback while raising concerns about academic integrity. This article provides a research informed, expert commentary to support new pharmacology educators in navigating this complex environment. The article is neither a systematic review by design and methodology, nor is it offering comprehensive coverage of the pertinent literature (an insurmountable task, given the breadth of the topic). We highlight how educators in basic and clinical pharmacology are transforming their teaching and curricula to enhance student success in current and future settings. Global initiatives, such as those sponsored by the International Union of Basic and Clinical Pharmacology, including the Pharmacology Education Project and Core Concepts-based curricula, are offering opportunities to enhance pharmacology education by standardizing key concepts, providing open-access learning resources, and fostering international collaboration. These efforts are intended to support alignment of curricula, improve student engagement through interactive materials, facilitating a global exchange of best practices, and supporting educators in adopting innovative teaching methodologies. These initiatives require contributions from pharmacology experts across multiple countries, languages, and cultures. Consequently, this article serves as a call to action to advance innovation and inclusivity in pharmacology education. SIGNIFICANCE STATEMENT: Recent disruptions in higher education have forced educators to adapt in ways that would have previously been unthinkable. The article provides an evidence-based, expert commentary for new pharmacology educators that will assist them to thrive in this complex environment.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 3","pages":"100126"},"PeriodicalIF":17.3,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778013","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}

{"title":"Disulfidptosis: A novel cell death mechanism with pathological significance and therapeutic potential in diseases.","authors":"Shaoju Qian, Lin Pan, Guanyu Chen, Fangfang Qiu, Yinghua Ma, Ruixue Li, Jawahar L Mehta, Xianwei Wang","doi":"10.1016/j.pharmr.2026.100127","DOIUrl":"https://doi.org/10.1016/j.pharmr.2026.100127","url":null,"abstract":"<p><p>Programmed cell death participates in diverse physiological and pathological processes. The identification of disulfidptosis reveals that disulfide stress-induced cytoskeletal disintegration constitutes a targetable biological process mediated through pathways such as SLC7A11-dependent cystine metabolism, offering potential therapeutic avenues for disease intervention. Disulfidptosis involves activation of specific molecular pathways, including SLC7A11-mediated cystine uptake, NADPH depletion, aberrant intracellular disulfide accumulation, filamentous actin collapse, and dysregulation of the antioxidant system, ultimately leading to cell death and contributing to disease progression. Furthermore, comparison between disulfidptosis and other established cell death modalities, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis, further underscores its unique biological characteristics and research significance, enabling intervention in disease progression. By targeting these pathways, we systematically integrated pharmacological agonists and inhibitors of key targets, such as SLC7A11-dependent cystine metabolism, to promote or inhibit disulfidptosis, thereby restoring cellular homeostasis disrupted by diseases including cancer, neurodegeneration, ischemia/reperfusion injury, autoimmune diseases, metabolic syndrome, and sepsis. This highlights the potential of disulfidptosis as a therapeutic target. We identified that therapeutic strategies targeting disulfidptosis converge on the core pathogenic axis of \"redox imbalance, disulfide stress, actin cytoskeleton collapse.\" These strategies exhibit disease-dependent bidirectionality-inducing disulfidptosis to selectively eliminate cancer cells in neoplastic diseases while suppressing this process to protect functional cells in non-neoplastic conditions. This review explores the current understanding of the molecular mechanisms and key regulatory nodes of disulfidptosis, deepening our comprehension of the role of disulfidptosis in human health and disease while revealing actionable targets and future research directions. SIGNIFICANCE STATEMENT: The discovery of disulfidptosis enriches understanding of programmed cell death, providing a foundation for targeting SLC7A11-mediated cystine metabolism and other key pathways to treat various diseases and offering new approaches for managing pathological processes previously considered intractable. As molecular mechanistic understanding advances, these emerging therapeutic strategies may open new research avenues, although clinical translation and efficacy require further validation.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 3","pages":"100127"},"PeriodicalIF":17.3,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444469","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}

{"title":"Emerging natural products against obesity and metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis: Direct target discovery and mechanistic insights.","authors":"Wei Hu, Meng Gu, Huibo Li, He Li, Juntao Kan, Lingli Zhang, Qian Ding, Yi Zhun Zhu","doi":"10.1016/j.pharmr.2026.100125","DOIUrl":"https://doi.org/10.1016/j.pharmr.2026.100125","url":null,"abstract":"<p><p>Obesity is a multifactorial metabolic condition characterized by dysregulated lipid accumulation and systemic energy imbalance with escalating global prevalence. This chronic disease drives a spectrum of life-threatening comorbidities, including metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), which now represent a primary cause of liver-related morbidity and transplantation. Both conditions share pathophysiological underpinnings such as insulin resistance, chronic inflammation, and mitochondrial dysfunction, creating a vicious cycle where obesity exacerbates hepatic steatosis and fibrosis. Although US Food and Drug Administration-approved antiobesity agents such as glucagon-like peptide-1 receptor agonists (eg, semaglutide) demonstrate weight loss efficacy, their long-term utility is constrained by gastrointestinal intolerance and variable effects on hepatic outcomes. Similarly, the recent approval of resmetirom for MASH, though groundbreaking, leaves unresolved challenges in durability, accessibility and some adverse effects including gastrointestinal reaction. The intricate molecular crosstalk linking adipose and hepatocyte dysfunction necessitates innovative therapeutics targeting shared pathophysiological pathways or novel molecular targets. Natural products, with inherent structural diversity and multitarget potential, offer a promising avenue for dual intervention in the obesity-MASH continuum. This review systematically evaluates emerging endogenous metabolites and plant-derived compounds, elucidating their directly validated molecular targets and preclinical evidence for metabolic reprogramming against obesity and MASLD/MASH. Furthermore, it synthesizes translational insights from natural product research and clinical trial experiences of related synthetic agonists. By integrating mechanistic discovery with a critical assessment of developmental challenges, this review aims to advance strategic frameworks for the concurrent management of obesity and MASLD/MASH. SIGNIFICANCE STATEMENT: Obesity-driven metabolic dysfunction-associated steatotic liver disease and steatohepatitis are leading causes of liver morbidity with limited treatment options. This review systematically evaluates natural products as multitarget therapeutics for these interconnected conditions. By integrating evidence of their efficacy and target mechanisms with modern discovery approaches, this study emphasizes pathways for clinical translation and aims to stimulate future research into novel, mechanism-based interventions.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 3","pages":"100125"},"PeriodicalIF":17.3,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639396","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}

{"title":"Regenerative therapeutics for chronic obstructive pulmonary disease.","authors":"Luke van der Koog, Henry R D Showell, Dyan F Nugraha, Mareike Lehmann, Thomas M Conlon, Ali Önder Yildirim, Rocío Fuentes-Mateos, Hoeke Baarsma, John-Poul Ng-Blichfeldt, Barbro N Melgert, Antonella F M Dost, Janette K Burgess, Stacy L S Yam, Irene H Heijink, Sidrah Ahmed, Margherita Paschini, Evalyne M Jansen, Wouter L J Hinrichs, Jill R Johnson, Xinhui Wu, Anika Nagelkerke, Henderik W Frijlink, Carla F Kim, Reinoud Gosens","doi":"10.1016/j.pharmr.2026.100124","DOIUrl":"https://doi.org/10.1016/j.pharmr.2026.100124","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases worldwide, characterized by an accelerated loss of lung function. A key problem underlying COPD is increased tissue destruction in combination with defective lung tissue repair. As current therapies do not modify the progression of the disease, new therapies aimed at restoring lung tissue repair in COPD need to be developed. In an attempt to address this major unmet need, there has been a surge in both preclinical and clinical studies, aiming to identify key mechanisms underpinning defective lung repair and the ability to inhibit or even reverse this defect. This includes small molecules such as retinoids, as well as advanced therapy medicinal products such as cell therapies or therapies with cell-derived products such as extracellular vesicles, or secreted proteins. The results of these endeavors have been variable with failures as well as successful proof-of-concepts. In this review, we provide an overview of the current state of the field, including modes of action of the therapeutics that are or have been considered for lung regeneration, including a discussion on the reasons for failure where relevant. In addition, we discuss hurdles in the clinical development of regenerative therapeutics for COPD including clinical outcomes, route of administration and formulation as these are pivotal considerations moving forward. SIGNIFICANCE STATEMENT: Chronic obstructive pulmonary disease is characterized by progressive alveolar destruction and defective epithelial regeneration. Targetable mechanisms, including cellular senescence, altered mesenchymal-epithelial signaling, and chronic inflammation, impair progenitor function and niche integrity. Therapeutic strategies that restore epithelial repair, including small molecules, biologics, and cell-based approaches, represent a promising path toward disease modification and long-term lung function restoration.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 3","pages":"100124"},"PeriodicalIF":17.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486962","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}

{"title":"Adhesion G protein-coupled receptors.","authors":"Tobias Langenhan, Garret R Anderson, Demet Araç, Gabriela Aust, Monserrat Avila-Zozaya, Sofie Morsing Bagger, Patrick Barth, Sandra Berndt, Stephen C Blacklow, Beatriz Blanco-Redondo, Antony A Boucard, James P Bridges, Lara-Sophie Brodmerkel, Kathleen M Caron, Yin Kwan Chung, Andrew N Dates, Virginea de Araujo Farias, Daniel Del Toro, Joseph G Duman, Felix B Engel, David M Favara, Caroline J Formstone, Chaoyu Fu, Alain Garcia De Las Bayonas, Anastasia Georgiadi, David E Gloriam, Randy A Hall, Jörg Hamann, Peter W Hildebrand, Cheng-Chih Hsiao, Bill X Huang, Jonathan A Javitch, Hee-Yong Kim, Robert J Kittel, Gunnar Kleinau, Richard Leduc, Ines Liebscher, Hsi-Hsien Lin, Joshua Linnert, Marie-Gabrielle Ludwig, David C Martinelli, Signe Mathiasen, Daniel Matúš, Mariam Melkumyan, Ana L Moreno-Salinas, Jan Mulder, Michael A Nash, Kasturi Pal, Daniel T Pederick, Nicole A Perry-Hauser, Xianhua Piao, Yu-Qi Ping, Dimitris G Placantonakis, Fabian Pohl, Simone Prömel, Mette M Rosenkilde, Laurent Sabbagh, Richard C Sando, Patrick Scheerer, Torsten Schöneberg, Elena Seiradake, Mareike Selcho, Florian Seufert, Abhishek K Singh, Georgios Skiniotis, Katja Spiess, Norbert Sträter, David Strutt, Thomas C Südhof, Jinpeng Sun, Gregory G Tall, Doreen Thor, Douglas G Tilley, Kimberley F Tolias, Mario Vallon, Erwin G Van Meir, Benoit Vanhollebeke, Giselle R Wiggin, Uwe Wolfrum, Jie Yan, Nathan A Zaidman, Yimin Zou, Nicole Scholz","doi":"10.1016/j.pharmr.2026.100116","DOIUrl":"10.1016/j.pharmr.2026.100116","url":null,"abstract":"<p><p>Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly apparent. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in this field and provides a comprehensive assessment of the current understanding of aGPCR biology, including a focus on human and mammalian aGPCRs, their evolutionary origins, methodological approaches, and model systems for their investigation, as well as emerging approaches for their therapeutic targeting. SIGNIFICANCE STATEMENT: Adhesion G protein-coupled receptors are versatile cell-surface proteins that integrate structural, biochemical, and physiological functions, with major roles in health and disease. This review summarizes current knowledge of their molecular features, functions in diverse model systems, and emerging opportunities for therapeutic targeting, providing a comprehensive resource that connects basic biology with translational applications across multiple scientific disciplines.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 3","pages":"100116"},"PeriodicalIF":17.3,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147531629","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}

{"title":"Edaravone: Advances on cytoprotective effects, pharmacological properties, and mechanisms of action.","authors":"Fatima Dakroub, Bassel Awada, Samar Abdelhady, Abdullah A Shaito, Ali H Eid, Joseph Walker, Stefania Mondello, Corina O Bondi, Federico Moro, Bahaa Elgendy, Kevin K Wang, Elisa R Zanier, Yehia Mechref, Firas Kobeissy","doi":"10.1016/j.pharmr.2025.100101","DOIUrl":"10.1016/j.pharmr.2025.100101","url":null,"abstract":"<p><p>Neurological diseases often lead to life-altering consequences, underscoring the urgent need for therapies that can reverse or mitigate their effects. Effective management of neurological disorders necessitates a thorough understanding of the common pathological mechanisms driving their onset and progression. Mitochondrial dysfunction and oxidative stress stand out as critical contributors to neuronal damage, implicated in traumatic brain injury, stroke, and amyotrophic lateral sclerosis. Disruptions in energy metabolism lead to the accumulation of reactive oxygen species and elevate the level of neural injury. Moreover, these imbalances disrupt cellular homeostasis and activate apoptotic pathways, further exacerbating neuronal loss and ultimately worsening the clinical prognosis. In this context, edaravone (Eda), a Food and Drug Administration-approved free radical scavenger, has emerged as a compelling candidate for the treatment of neuropathologies. This review provides a comprehensive overview of Eda, detailing its chemical structure and pharmacokinetic profile, with a focus on strategies to enhance its delivery to the central nervous system by modulating blood-brain barrier permeability or employing delivery systems that facilitate central nervous system penetration. Moreover, the review examines Eda's pharmacodynamic properties, including the signaling pathways it influences. The neurotherapeutic potential of Eda is further examined through in vitro and in vivo models of neurological disease. Insights from clinical trials are discussed to bridge the gap between preclinical findings and patient outcomes. Finally, the review highlights the synergistic effects of combining Eda with other pharmacological agents or therapeutic interventions, underscoring its promise as a versatile and indispensable treatment for neurological disorders. SIGNIFICANCE STATEMENT: Edaravone, a Food and Drug Administration-approved free radical scavenger, shows broad neuroprotective potential by mitigating oxidative stress and mitochondrial dysfunction across diverse neurological disorders, including stroke, amyotrophic lateral sclerosis, and traumatic brain injury. By synthesizing preclinical and clinical evidence, this review highlights edaravone's pleiotropic therapeutic actions, identifies translational challenges, and underscores its promise as a versatile treatment strategy for neurodegenerative and acute and chronic brain conditions.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 1","pages":"100101"},"PeriodicalIF":17.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605401","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}

{"title":"Genetic therapies for neurological diseases.","authors":"Ahad A Rahim, Manju A Kurian, Haiyan Zhou, Ross Ferguson, Sarah J Tabrizi, Gabriele Lignani, Kristian Aquilina, Simon N Waddington","doi":"10.1016/j.pharmr.2025.100093","DOIUrl":"10.1016/j.pharmr.2025.100093","url":null,"abstract":"<p><p>Often, gene therapy reviews concentrate upon specific therapeutic modalities-particularly either viral vector-mediated or a nonviral approach. Here, we draw together a comprehensive array of knowledge across the field of genetic therapy for genetic neurological disease. The sections on preclinical and clinical application of viral vectors are followed by sections on RNA-based therapies and then by antisense oligonucleotide approaches also in preclinical and clinical settings. We present a separate section on gene editing strategies and conclude with a section elaborating on the neurosurgical techniques and the expertise required for clinical application of many of these technologies. SIGNIFICANCE STATEMENT: Genetic therapies have significant potential to treat life-limiting neurological diseases. This review examines the different approaches, clinical successes, and considerations on how to deploy them.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 1","pages":"100093"},"PeriodicalIF":17.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12881687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752018","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}

{"title":"Waking up to the evidence of pharmacological treatments used to manage sleep disorders in people with dementia and mild cognitive impairment-A scoping review.","authors":"Bandana Saini, Shawn D X Kong, Zoe Menczel Schrire, Laura H Jacobson, Ron Grunstein, Sharon L Naismith","doi":"10.1016/j.pharmr.2025.100094","DOIUrl":"10.1016/j.pharmr.2025.100094","url":null,"abstract":"<p><p>Sleep disturbance is increasingly recognized as a viable prevention target that could lower dementia risk. While a wide range of pharmacological options exist to manage sleep disturbance in people living with dementia, their use often does not adherent to the quality use of medicine. The complex nature of dementia as a syndrome often requires drugs that target multiple complaints (eg, sleep, cognition, and mood) and thus could produce psychological and physiological side effects that have the potential to do more harm than confer benefits. Therefore, this review first provides an expert narration of the pharmacology of sleep and the mechanisms of agents used to treat sleep disturbance. Then, a systematic scoping review was conducted to analyze evidence from studies over the past 10 years, which examined various pharmacological agents used for sleep disturbance in people living with dementia. SIGNIFICANCE STATEMENT: Sleep disturbances are a common consequence of the neurodegenerative changes occurring in dementia syndromes. They may also be etiologically linked to its development and progression. This review summarizes the pharmacological basis of sleep and collates the impact of medications used for dementia or sedatives on sleep and cognition outcomes. The review highlights gaps in research and will provide clinicians with key information required to make decisions about the quality use of medications to improve sleep health in those with dementia.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 1","pages":"100094"},"PeriodicalIF":17.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605443","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}

{"title":"miR-155 aberrant expression impairs tumor rejection because of its targeting of ICOSL and multiple pathways implicated in the antitumor response.","authors":"Esmerina Tili, Jean-Jacques Michaille, Carlo M Croce","doi":"10.1016/j.pharmr.2025.100088","DOIUrl":"10.1016/j.pharmr.2025.100088","url":null,"abstract":"<p><p>Cancer treatments have dramatically improved because of advances in surgery, radiotherapy, and chemotherapy. Although the duration of remission has steadily increased in recent years, preventing metastasis and achieving complete remission is still beyond reach for various types of cancers. However, recent advancements in immunology have facilitated the development of immunotherapies aimed at enhancing the specificity and efficacy of natural anticancer immune responses while impairing the inhibitory effects of immune checkpoints. Although immunotherapies combined with other treatment modalities have already produced remarkable results in previously untreatable tumors, many patients still do not achieve complete remission. In this review, we explore the effects of miR-155, a microRNA that plays a critical role in initiation and resolution of both innate and adaptive immunity. Among the many target transcripts of miR-155 are those encoding immune checkpoints, cell cycle regulators, epigenetics regulators, transcription factors, DNA repairs factors, and factors involved in various signaling pathways. The inhibitory effects of miR-155 on its target transcripts are likely to be context- and dose-dependent. As certain miR-155 targets can have opposing effects based on their dose and activity, therapies aimed at increasing or decreasing miR-155 levels can potentially backfire, inhibiting the beneficial effects of widely used anticancer drugs. Precise monitoring and adjustment of miR-155 levels, depending on the type and stage of tumors, should enhance the effectiveness of immunotherapies and increase the percentage of patients achieving complete remission in the future, particularly when immunotherapies are combined with chemotherapies. SIGNIFICANCE STATEMENT: Although immunotherapies developed the last decade have brought hope and improved cancer treatments, prevented metastasis, and increased the rate of complete remission, many aspects of the anticancer immune response are controlled by miR-155, a microRNA whose activity is both context- and dose-dependent. Therefore, it is essential to determine the optimal levels of miR-155 activity according to the type and stage of tumors, in order to fully unlock the potential of immunotherapies in combination with surgery, radiotherapies, or chemotherapies.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":"78 1","pages":"100088"},"PeriodicalIF":17.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12881686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605432","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}