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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
From “contraindicated” to “first line” – Current mechanistic insights beyond canonical β-receptor signaling 从 "禁忌症 "到 "一线治疗"--当前超越典型β受体信号转导的机理认识
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-04-17 DOI: 10.1016/j.coph.2024.102458
Theresa Brand , Ann-Kathrin Lukannek , Valérie Jahns , Roland Jahns , Kristina Lorenz
{"title":"From “contraindicated” to “first line” – Current mechanistic insights beyond canonical β-receptor signaling","authors":"Theresa Brand ,&nbsp;Ann-Kathrin Lukannek ,&nbsp;Valérie Jahns ,&nbsp;Roland Jahns ,&nbsp;Kristina Lorenz","doi":"10.1016/j.coph.2024.102458","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102458","url":null,"abstract":"<div><p>β-blockers are a solid pillar in the treatment of cardiovascular diseases. However, they are highly discussed regarding effectiveness for certain indications and side-effects. Even though there are up to 20 licensed compounds, only four are used for heart failure (HF) therapy. On the receptor level several key characteristics seem to influence the clinical outcome: subtype selectivity, antagonistic vs (inverse/biased) agonistic properties and -in particular- ancillary capacities. On a molecular level, divergent and novel signaling patterns are being identified and extra-cardiac effects on e.g. inflammation, metabolism and oxidative stress are highlighted. This review discusses different well-known and newly discovered characteristics that need to be considered for HF therapy and in the context of co-morbidities.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"76 ","pages":"Article 102458"},"PeriodicalIF":4.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1471489224000286/pdfft?md5=79cdbcebcc1144f5a8184b3d624ad690&pid=1-s2.0-S1471489224000286-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140607315","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
The complement pathway as a therapeutic target for neovascular age-related macular degeneration-mediated subretinal fibrosis 补体途径是新生血管性老年黄斑变性介导的视网膜下纤维化的治疗靶点
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-03-30 DOI: 10.1016/j.coph.2024.102448
Heping Xu , Caijiao Yi , Mei Chen
{"title":"The complement pathway as a therapeutic target for neovascular age-related macular degeneration-mediated subretinal fibrosis","authors":"Heping Xu ,&nbsp;Caijiao Yi ,&nbsp;Mei Chen","doi":"10.1016/j.coph.2024.102448","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102448","url":null,"abstract":"<div><p>Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in the elderly in developed countries. Intravitreal injection of VEGF inhibitors is the mainstream therapy for nAMD, although nearly 50% of the patients do not respond or respond poorly to the therapy. One of the main reasons for the poor outcome of the therapy is the development of subretinal macular fibrosis, a process of excessive deposition of extracellular matrix proteins around the diseased blood vessels. Currently, there is no medication to prevent or treat the condition. Here, we discussed recent advances in the pathogenesis of nAMD-mediated macular fibrosis, with a focus on the role of the complement system. We further proposed approaches to target the complement system for the management of macular fibrosis and highlighted the area of further research for future clinical applications of complement-based therapy.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"76 ","pages":"Article 102448"},"PeriodicalIF":4.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1471489224000183/pdfft?md5=fbf295b621546072e3f80c3a7d39177b&pid=1-s2.0-S1471489224000183-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140328504","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
Targeting TRP channels for pain relief: A review of current evidence from bench to bedside 靶向 TRP 通道缓解疼痛：从临床到床边的现有证据综述
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-03-11 DOI: 10.1016/j.coph.2024.102447
Ari-Pekka Koivisto , Thomas Voets , Michael J. Iadarola , Arpad Szallasi
{"title":"Targeting TRP channels for pain relief: A review of current evidence from bench to bedside","authors":"Ari-Pekka Koivisto ,&nbsp;Thomas Voets ,&nbsp;Michael J. Iadarola ,&nbsp;Arpad Szallasi","doi":"10.1016/j.coph.2024.102447","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102447","url":null,"abstract":"<div><p>Several decades of research support the involvement of transient receptor potential (TRP) channels in nociception. Despite the disappointments of early TRPV1 antagonist programs, the TRP family remains a promising therapeutic target in pain disorders. High-dose capsaicin patches are already in clinical use to relieve neuropathic pain. At present, localized injections of the side-directed TRPV1 agonist capsaicin and resiniferatoxin are undergoing clinical trials in patients with osteoarthritis and bone cancer pain. TRPA1, TRPM3, and TRPC5 channels are also of significant interest. This review discusses the role of TRP channels in human pain conditions.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"75 ","pages":"Article 102447"},"PeriodicalIF":4.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1471489224000171/pdfft?md5=e71d630d360072b78e623fcc3092cb04&pid=1-s2.0-S1471489224000171-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095804","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
Estrogen related receptor alpha: Potential modulator of age-related macular degeneration 雌激素相关受体α：老年性黄斑变性的潜在调节剂
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2024-03-05 DOI: 10.1016/j.coph.2024.102439
Fatima Massare Somers , Goldis Malek
{"title":"Estrogen related receptor alpha: Potential modulator of age-related macular degeneration","authors":"Fatima Massare Somers ,&nbsp;Goldis Malek","doi":"10.1016/j.coph.2024.102439","DOIUrl":"https://doi.org/10.1016/j.coph.2024.102439","url":null,"abstract":"<div><p>To develop effective therapies for complex blinding diseases such as age-related macular degeneration (AMD), identification of mechanisms involved in its initiation and progression is needed. The estrogen-related receptor alpha (ESRRA) is an orphan nuclear receptor that regulates several AMD-associated pathogenic pathways. However, it has not been investigated in detail in the ocular posterior pole during aging or in AMD. This review delves into the literature highlighting the significance of ESRRA as a molecular target that may be important in the pathobiology of AMD, and discusses data available supporting the targeting of this receptor signaling pathway as a therapeutic option for AMD.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"75 ","pages":"Article 102439"},"PeriodicalIF":4.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140030406","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
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