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Current Opinion in Pharmacology最新文献

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Drug effects on neuropeptides and their receptors: Big hopes but moderate success in the treatment of chronic pain 药物对神经肽及其受体的影响：在治疗慢性疼痛方面希望很大，但成效一般。
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-08-01 DOI: 10.1016/j.coph.2024.102474
Éva Borbély , Gábor Pethő
{"title":"Drug effects on neuropeptides and their receptors: Big hopes but moderate success in the treatment of chronic pain","authors":"Éva Borbély ,&nbsp;Gábor Pethő","doi":"10.1016/j.coph.2024.102474","DOIUrl":"10.1016/j.coph.2024.102474","url":null,"abstract":"<div><p>Neuropeptides, including tachykinins, CGRP, and somatostatin, are localized in a peptidergic subgroup of nociceptive primary afferent neurons. Tachykinins and CGRP are pronociceptive, somatostatin is an antinociceptive mediator. Intensive drug research has been performed to develop tachykinin and CGRP antagonists, and somatostatin agonists as analgesics. CGRP receptor antagonists are efficacious and well-tolerated drugs in migraine. Monoclonal antibodies against CGRP or its receptor are used for the prophylactic treatment of migraine. Tachykinin NK<sub>1</sub> receptor antagonists failed as analgesics but are used for chemotherapy-induced nausea and vomiting. New, orally active somatostatin 4 receptor agonists are promising drug candidates for treating various pain conditions.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"77 ","pages":"Article 102474"},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1471489224000444/pdfft?md5=2c673f991bfcf2fb2e89749522e229b8&pid=1-s2.0-S1471489224000444-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Modulating regulatory T cell migration in the treatment of autoimmunity and autoinflammation 调节调节性 T 细胞迁移以治疗自身免疫和自身炎症
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-06-20 DOI: 10.1016/j.coph.2024.102466
John Martin , Zoe Hollowood , Jamie Chorlton , Carlene Dyer , Federica Marelli-Berg
{"title":"Modulating regulatory T cell migration in the treatment of autoimmunity and autoinflammation","authors":"John Martin ,&nbsp;Zoe Hollowood ,&nbsp;Jamie Chorlton ,&nbsp;Carlene Dyer ,&nbsp;Federica Marelli-Berg","doi":"10.1016/j.coph.2024.102466","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102466","url":null,"abstract":"<div><p>Treatment of autoimmunity and autoinflammation with regulatory T cells has received much attention in the last twenty years. Despite the well-documented clinical benefit of Treg therapy, a large-scale application has proven elusive, mainly due to the extensive culture facilities required and associated costs. A possible way to overcome these hurdles in part is to target Treg migration to inflammatory sites using a small molecule. Here we review recent advances in this strategy and introduce the new concept of pharmacologically enhanced delivery of endogenous Tregs to control inflammation, which has been recently validated in humans.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"77 ","pages":"Article 102466"},"PeriodicalIF":4.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Pharmacological regulation of HIF-1α, RGC death, and glaucoma 对 HIF-1α、RGC 死亡和青光眼的药理调节
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-06-18 DOI: 10.1016/j.coph.2024.102467
Shahid Husain, Ryan Leveckis
{"title":"Pharmacological regulation of HIF-1α, RGC death, and glaucoma","authors":"Shahid Husain,&nbsp;Ryan Leveckis","doi":"10.1016/j.coph.2024.102467","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102467","url":null,"abstract":"<div><p>Hypoxia can regulate oxygen-sensitive pathways that could be neuroprotective to compensate for the detrimental effects of low oxygen. However, prolonged hypoxia can activate neurodegenerative pathways. HIF-1α is upregulated/stabilized in hypoxic conditions, promoting alteration of gene expression, and ultimately leading to cell-death. Therefore, regulation of HIF-1α expression pharmacologically is a vital approach to mitigate cell death. In this review, we provide information showing the role of HIF-1α and its associated pathways in ocular retinopathies. We also discuss the beneficial roles of HIF-1α inhibitor, KC7F2, in ocular pathologies. Finally, we provided our own data demonstrating RGC neuroprotection by KC7F2 in glaucomatous animals.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"77 ","pages":"Article 102467"},"PeriodicalIF":4.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Biased signalling in analgesic research and development 镇痛药研发中的偏差信号。
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-06-01 DOI: 10.1016/j.coph.2024.102465
Alexandra Conibear , Chris P. Bailey , Eamonn Kelly
{"title":"Biased signalling in analgesic research and development","authors":"Alexandra Conibear ,&nbsp;Chris P. Bailey ,&nbsp;Eamonn Kelly","doi":"10.1016/j.coph.2024.102465","DOIUrl":"10.1016/j.coph.2024.102465","url":null,"abstract":"<div><p>Ligand bias offers a novel means to improve the therapeutic profile of drugs. With regard to G protein-coupled receptors involved in analgesia, it could be advantageous to develop such drugs if the analgesic effect is mediated by a different cellular signalling pathway than the adverse effects associated with the drug. Whilst this has been explored over a number of years for the μ receptor, it remains unclear whether this approach offers significant benefit for the treatment of pain. Nevertheless, the development of biased ligands at other G protein-coupled receptors in the CNS does offer some promise for the development of novel analgesic drugs in the future. Here we summarise and discuss the recent evidence to support this.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"76 ","pages":"Article 102465"},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1471489224000353/pdfft?md5=32e81c305fc6f36f94d7422b87926a4d&pid=1-s2.0-S1471489224000353-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Effects of protein glycation and protective mechanisms against glycative stress 蛋白质糖化的影响和糖化应激的保护机制
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-05-25 DOI: 10.1016/j.coph.2024.102464
Jade A. Najjar, John W. Calvert
{"title":"Effects of protein glycation and protective mechanisms against glycative stress","authors":"Jade A. Najjar,&nbsp;John W. Calvert","doi":"10.1016/j.coph.2024.102464","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102464","url":null,"abstract":"<div><p>Glycation is a posttranslational modification of proteins that contributes to the vast array of biological information that can be conveyed via a singular proteome. Understanding the role of advanced glycation end-products (AGEs) in human health and pathophysiology can be difficult, as the physiological effects of AGEs have been associated with multiple biological processes and disease state development, including acute myocardial ischemia-reperfusion injury, heart failure, and atherosclerosis, as well as tumor cell migration. The critical role of the glyoxalase system in the detoxification of methylglyoxal and other AGEs has been well established. Recently, evidence has emerged that DJ-1 displays antiglycative activity and may contribute to another mechanism of protection against protein glycation outside of the glyoxalase system. Identification of potential substrates of DJ-1 and determination of the pathways in which DJ-1 operates, is needed to fully understand the role of this protein in modulating biological homeostasis and the development of disease.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"76 ","pages":"Article 102464"},"PeriodicalIF":4.0,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141095837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Pharmaceutical therapies targeting autophagy for the treatment of age-related macular degeneration 治疗老年性黄斑变性的自噬药物疗法
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-05-23 DOI: 10.1016/j.coph.2024.102463
Kirstan A. Vessey , Andrew I. Jobling , Ursula Greferath , Erica L. Fletcher
{"title":"Pharmaceutical therapies targeting autophagy for the treatment of age-related macular degeneration","authors":"Kirstan A. Vessey ,&nbsp;Andrew I. Jobling ,&nbsp;Ursula Greferath ,&nbsp;Erica L. Fletcher","doi":"10.1016/j.coph.2024.102463","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102463","url":null,"abstract":"<div><p>Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in the elderly. Although new therapies have recently emerged, there are currently no ways of preventing the development of the disease. Changes in intracellular recycling processes. Changes in intracellular recycling processes, called autophagy, lead to debris accumulation and cellular dysfunction in AMD models and AMD patients. Drugs that enhance autophagy hold promise as therapies for slowing AMD progression in preclinical models; however, more studies in humans are required. While a definitive cure for AMD will likely hinge on a personalized medicine approach, treatments that enhance autophagy hold promise for slowing vision loss.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"76 ","pages":"Article 102463"},"PeriodicalIF":4.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S147148922400033X/pdfft?md5=c1fdb8a022f5d9240b466a585108e84b&pid=1-s2.0-S147148922400033X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141091024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Shaping DNA damage responses: Therapeutic potential of targeting telomeric proteins and DNA repair factors in cancer 塑造 DNA 损伤反应：针对癌症端粒蛋白和 DNA 修复因子的治疗潜力
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-05-21 DOI: 10.1016/j.coph.2024.102460
Yu Bin Ng, Semih Can Akincilar
{"title":"Shaping DNA damage responses: Therapeutic potential of targeting telomeric proteins and DNA repair factors in cancer","authors":"Yu Bin Ng,&nbsp;Semih Can Akincilar","doi":"10.1016/j.coph.2024.102460","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102460","url":null,"abstract":"<div><p>Shelterin proteins regulate genomic stability by preventing inappropriate DNA damage responses (DDRs) at telomeres. Unprotected telomeres lead to persistent DDR causing cell cycle inhibition, growth arrest, and apoptosis. Cancer cells rely on DDR to protect themselves from DNA lesions and exogenous DNA-damaging agents such as chemotherapy and radiotherapy. Therefore, targeting DDR machinery is a promising strategy to increase the sensitivity of cancer cells to existing cancer therapies. However, the success of these DDR inhibitors depends on other mutations, and over time, patients develop resistance to these therapies. This suggests the need for alternative approaches. One promising strategy is co-inhibiting shelterin proteins with DDR molecules, which would offset cellular fitness in DNA repair in a mutation-independent manner. This review highlights the associations and dependencies of the shelterin complex with the DDR proteins and discusses potential co-inhibition strategies that might improve the therapeutic potential of current inhibitors.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"76 ","pages":"Article 102460"},"PeriodicalIF":4.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141078200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Editorial overview: Special issue on “Rheumatology: Therapeutic advances for autoimmune and musculoskeletal diseases” 编辑综述：风湿病学》特刊：自身免疫性疾病和肌肉骨骼疾病的治疗进展 "特刊。
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-05-18 DOI: 10.1016/j.coph.2024.102462
Larry W. Moreland, Kristine Kuhn
{"title":"Editorial overview: Special issue on “Rheumatology: Therapeutic advances for autoimmune and musculoskeletal diseases”","authors":"Larry W. Moreland,&nbsp;Kristine Kuhn","doi":"10.1016/j.coph.2024.102462","DOIUrl":"10.1016/j.coph.2024.102462","url":null,"abstract":"","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"76 ","pages":"Article 102462"},"PeriodicalIF":4.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
In the heart and beyond: Mitochondrial dysfunction in heart failure with preserved ejection fraction (HFpEF) 心脏内外：射血分数保留型心力衰竭（HFpEF）的线粒体功能障碍
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-05-16 DOI: 10.1016/j.coph.2024.102461
Nisha Bhattarai , Iain Scott
{"title":"In the heart and beyond: Mitochondrial dysfunction in heart failure with preserved ejection fraction (HFpEF)","authors":"Nisha Bhattarai ,&nbsp;Iain Scott","doi":"10.1016/j.coph.2024.102461","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102461","url":null,"abstract":"<div><p>Heart failure with preserved ejection fraction (HFpEF) is a major cardiovascular disorder with increasing prevalence and a limited range of targeted treatment options. While HFpEF can be derived from several different etiologies, much of the current growth in the disease is being driven by metabolic dysfunction (e.g. obesity, diabetes, hypertension). Deleterious changes in mitochondrial energy metabolism are a common feature of HFpEF, and may help to drive the progression of the disease. In this brief article we aim to review various aspects of cardiac mitochondrial dysfunction in HFpEF, discuss the emerging topic of HFpEF-driven mitochondrial dysfunction in tissues beyond the heart, and examine whether supporting mitochondrial function may be a therapeutic approach to arrest or reverse disease development.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"76 ","pages":"Article 102461"},"PeriodicalIF":4.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140950058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Advanced therapeutic approaches in sarcoglycanopathies 肌糖蛋白病的先进治疗方法
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-05-06 DOI: 10.1016/j.coph.2024.102459
Martina Scano, Alberto Benetollo, Francesco Dalla Barba, Dorianna Sandonà
{"title":"Advanced therapeutic approaches in sarcoglycanopathies","authors":"Martina Scano,&nbsp;Alberto Benetollo,&nbsp;Francesco Dalla Barba,&nbsp;Dorianna Sandonà","doi":"10.1016/j.coph.2024.102459","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102459","url":null,"abstract":"<div><p>Sarcoglycanopathies are rare autosomal recessive diseases belonging to the family of limb-girdle muscular dystrophies. They are caused by mutations in the genes coding for α-, β-, γ-, and δ-sarcoglycan. The mutations impair the assembly of a key structural complex, which normally protects the sarcolemma of striated muscle from contraction-derived stress. Although heterogeneous, sarcoglycanopathies are characterized by progressive muscle degeneration, increased serum creatine kinase levels, loss of ambulation often during adolescence, and variable cardio-respiratory impairment. Genetic defects can impair sarcoglycan synthesis or produce a protein that is defective in folding. There is currently no effective treatment available; however, both gene replacement strategy and small molecule-based approaches show great promise and have entered or are starting to enter clinical trials.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"76 ","pages":"Article 102459"},"PeriodicalIF":4.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1471489224000298/pdfft?md5=796d4540be847c3a29a21c32b5e60938&pid=1-s2.0-S1471489224000298-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140842791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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