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Spatiotemporal GPCR signaling illuminated by genetically encoded fluorescent biosensors 基因编码荧光生物传感器照射的时空GPCR信号
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-08-01 DOI: 10.1016/j.coph.2023.102384
Charlotte Kayser , Barbora Melkes , Cécile Derieux , Andreas Bock
{"title":"Spatiotemporal GPCR signaling illuminated by genetically encoded fluorescent biosensors","authors":"Charlotte Kayser ,&nbsp;Barbora Melkes ,&nbsp;Cécile Derieux ,&nbsp;Andreas Bock","doi":"10.1016/j.coph.2023.102384","DOIUrl":"10.1016/j.coph.2023.102384","url":null,"abstract":"<div><p><span>G protein-coupled receptors (GPCRs) are ligand-activated cell membrane proteins and represent the most important class of drug targets. GPCRs adopt several active conformations that stimulate different intracellular </span>G proteins<span> (and other transducers) and thereby modulate second messenger levels, eventually resulting in receptor-specific cell responses. It is increasingly accepted that not only the type of active signaling protein but also the duration of its stimulation and the subcellular location from where receptors signal distinctly contribute to the overall cell response. However, the molecular principles governing such spatiotemporal GPCR signaling and their role in disease are incompletely understood. Genetically encoded, fluorescent biosensors—in particular for the GPCR/cAMP signaling axis—have been pivotal to the discovery and molecular understanding of novel concepts in spatiotemporal GPCR signaling. These include GPCR priming, location bias, and receptor-associated independent cAMP nanodomains. Here, we review such technologies that we believe will illuminate the spatiotemporal organization of other GPCR signaling pathways that define the complex signaling architecture of the cell.</span></p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9920447","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: 2
Central and peripheral mechanisms involved in the control of GnRH neuronal function by metabolic factors 代谢因子控制GnRH神经元功能的中枢和外周机制
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-08-01 DOI: 10.1016/j.coph.2023.102382
Miguel Ruiz-Cruz , Carmen Torres-Granados , Manuel Tena-Sempere , Juan Roa
{"title":"Central and peripheral mechanisms involved in the control of GnRH neuronal function by metabolic factors","authors":"Miguel Ruiz-Cruz ,&nbsp;Carmen Torres-Granados ,&nbsp;Manuel Tena-Sempere ,&nbsp;Juan Roa","doi":"10.1016/j.coph.2023.102382","DOIUrl":"10.1016/j.coph.2023.102382","url":null,"abstract":"<div><p>Gonadotropin-releasing hormone (GnRH) neurons are the final output pathway for the brain control of reproduction. The activity of this neuronal population, mainly located at the preoptic area of the hypothalamus, is controlled by a plethora of metabolic signals. However, it has been documented that most of these signal impact on GnRH neurons through indirect neuronal circuits, Kiss1, proopiomelanocortin, and neuropeptide Y/agouti-related peptide neurons being some of the most prominent mediators. In this context, compelling evidence has been gathered in recent years on the role of a large range of neuropeptides and energy sensors in the regulation of GnRH neuronal activity through both direct and indirect mechanisms. The present review summarizes some of the most prominent recent advances in our understanding of the peripheral factors and central mechanisms involved in the metabolic control of GnRH neurons.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9971557","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
Corrigendum to “Antihypertensive effect of soybean bioactive peptides: A review” [Curr Opin Pharmacol (62) (2022) 74–81] 更正“大豆生物活性肽的降压作用：综述”[Curr Opin Pharmacol（62）（2022）74-81]
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-08-01 DOI: 10.1016/j.coph.2023.102383
Tingna Li , Xiaorui Zhang , Yuanyuan Ren , Yijia Zeng , Qinwan Huang , Chao Wang
{"title":"Corrigendum to “Antihypertensive effect of soybean bioactive peptides: A review” [Curr Opin Pharmacol (62) (2022) 74–81]","authors":"Tingna Li ,&nbsp;Xiaorui Zhang ,&nbsp;Yuanyuan Ren ,&nbsp;Yijia Zeng ,&nbsp;Qinwan Huang ,&nbsp;Chao Wang","doi":"10.1016/j.coph.2023.102383","DOIUrl":"10.1016/j.coph.2023.102383","url":null,"abstract":"","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268434","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
Targeting cAMP signaling compartments in iPSC-derived models of cardiovascular disease iPSC衍生的心血管疾病模型中的靶向cAMP信号区
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-08-01 DOI: 10.1016/j.coph.2023.102392
Tiannan Liu , Enno Klussmann
{"title":"Targeting cAMP signaling compartments in iPSC-derived models of cardiovascular disease","authors":"Tiannan Liu ,&nbsp;Enno Klussmann","doi":"10.1016/j.coph.2023.102392","DOIUrl":"10.1016/j.coph.2023.102392","url":null,"abstract":"<div><p>Adenosine 3′,5′-cyclic monophosphate (cAMP) acts as a second messenger that is involved in the regulation of a plethora of processes. The activation of cAMP signaling in defined compartments is critical for cells to respond to an extracellular stimulus in a specific manner. Rapid advances in the field of human induced pluripotent stem cells (iPSCs) reflect their great potential for cardiovascular disease modeling, drug screening, regenerative and precision medicine. This review discusses cAMP signaling in iPSC-derived cardiovascular disease models, and the prospects of using such systems to elucidate disease mechanisms, drug actions and to identify novel drug targets for the treatment of cardiovascular diseases with unmet medical need, such as hypertension and heart failure.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9918379","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
Spinal and bulbar muscular atrophy: From molecular pathogenesis to pharmacological intervention targeting skeletal muscle 脊髓和延髓肌萎缩：从分子发病机制到针对骨骼肌的药物干预
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-08-01 DOI: 10.1016/j.coph.2023.102394
Caterina Marchioretti , Roberta Andreotti , Emanuela Zuccaro , Andrew P. Lieberman , Manuela Basso , Maria Pennuto
{"title":"Spinal and bulbar muscular atrophy: From molecular pathogenesis to pharmacological intervention targeting skeletal muscle","authors":"Caterina Marchioretti ,&nbsp;Roberta Andreotti ,&nbsp;Emanuela Zuccaro ,&nbsp;Andrew P. Lieberman ,&nbsp;Manuela Basso ,&nbsp;Maria Pennuto","doi":"10.1016/j.coph.2023.102394","DOIUrl":"10.1016/j.coph.2023.102394","url":null,"abstract":"<div><p>The clinical characteristics of SBMA, also known as Kennedy's disease (OMIM 313200), were initially documented by Dr. H Kawahara in the 18th century and a hundred years later by Dr. W. Kennedy. SBMA is a neuromuscular disease caused by expansions of a CAG microsatellite tandem repeat in exon 1 of the androgen receptor (<em>AR</em>) gene located on the X chromosome. These expansions result in the production of AR with an aberrantly expanded polyglutamine (polyQ) tract. In this review, we explore recent advancements in the significance of gene expression changes in skeletal muscle and discuss how pharmacological interventions targeting this aspect of disease pathogenesis can potentially be translated into therapies for SBMA patients.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9909288","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
Adenosine signaling as target in cardiovascular pharmacology 腺苷信号传导作为心血管药理学的靶点。
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-08-01 DOI: 10.1016/j.coph.2023.102393
Luca Antonioli , Matteo Fornai , Carolina Pellegrini , Pál Pacher , György Haskó
{"title":"Adenosine signaling as target in cardiovascular pharmacology","authors":"Luca Antonioli ,&nbsp;Matteo Fornai ,&nbsp;Carolina Pellegrini ,&nbsp;Pál Pacher ,&nbsp;György Haskó","doi":"10.1016/j.coph.2023.102393","DOIUrl":"10.1016/j.coph.2023.102393","url":null,"abstract":"<div><p><span><span>Increasing evidence demonstrated the relevance of adenosine system in the onset and development of cardiovascular diseases, such as hypertension, myocardial infarct, ischemia, hypertension, heart failure, and atherosclerosis. In this regard, intense research efforts are being focused on the characterization of the pathophysiological significance of adenosine, acting at its </span>membrane receptors named A</span><sub>1</sub>, A<sub>2A</sub>, A<sub>2B</sub>, and A<sub>3</sub><span> receptors, in cardiovascular diseases. The present review article provides an integrated and comprehensive overview about current clinical and pre-clinical evidence about the role of adenosine in the pathophysiology of cardiovascular diseases. Particular attention has been focused on current scientific evidence about the pharmacological ligands acting on adenosine pathway as useful tools to manage cardiovascular diseases.</span></p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10356992","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
NMR applications to GPCR recognition by peptide ligands NMR在肽配体GPCR识别中的应用
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-06-01 DOI: 10.1016/j.coph.2023.102366
Kazem Asadollahi , Daniel J. Scott , Paul R. Gooley
{"title":"NMR applications to GPCR recognition by peptide ligands","authors":"Kazem Asadollahi ,&nbsp;Daniel J. Scott ,&nbsp;Paul R. Gooley","doi":"10.1016/j.coph.2023.102366","DOIUrl":"10.1016/j.coph.2023.102366","url":null,"abstract":"<div><p>Peptides form the largest group of ligands that modulate the activity of more than 120 different GPCRs. Among which linear disordered peptide ligands usually undergo significant conformational changes upon binding that is essential for receptor recognition and activation. Conformational selection and induced fit are the extreme mechanisms of coupled folding and binding that can be distinguished by analysis of binding pathways by methods that include NMR. However, the large size of GPCRs in membrane-mimetic environments limits NMR applications. In this review, we highlight advances in the field that can be adopted to address coupled folding and binding of peptide ligands to their cognate receptors.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9603082","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
Purinergic signaling pathway in severe COVID-19 重症新冠肺炎的嘌呤能信号通路
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-06-01 DOI: 10.1016/j.coph.2023.102379
Lourdes Arruvito, Inés Sananez, Vanesa Seery, Constanza Russo, Jorge Geffner
{"title":"Purinergic signaling pathway in severe COVID-19","authors":"Lourdes Arruvito,&nbsp;Inés Sananez,&nbsp;Vanesa Seery,&nbsp;Constanza Russo,&nbsp;Jorge Geffner","doi":"10.1016/j.coph.2023.102379","DOIUrl":"10.1016/j.coph.2023.102379","url":null,"abstract":"<div><p>Substantial efforts have been made to understand the immune response during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, in order to identify and characterize risk factors, immune mechanisms responsible for the induction of tissue injury and potential therapeutic targets. Purinergic signaling pathway has shown to modulate the inflammatory processes in the course of several infectious diseases, but its role in the coronavirus disease 2019 (COVID-19) has not been clearly defined. Inflammation is usually associated to the release of ATP from different cell types, starting a cascade of events through the activation of a set of different purinergic receptors. This review summarizes the evidence showing the involvement of the purinergic system in the inflammatory condition that characterizes severe COVID-19.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9605008","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
Considerations for individualized first-line systemic treatment in advanced hepatocellular carcinoma 晚期肝细胞癌个体化一线系统治疗的思考
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-06-01 DOI: 10.1016/j.coph.2023.102365
Frederik Peeters, Jeroen Dekervel
{"title":"Considerations for individualized first-line systemic treatment in advanced hepatocellular carcinoma","authors":"Frederik Peeters,&nbsp;Jeroen Dekervel","doi":"10.1016/j.coph.2023.102365","DOIUrl":"10.1016/j.coph.2023.102365","url":null,"abstract":"<div><p><span><span>Primary liver cancer is the third most common cause of cancer-related death worldwide and hepatocellular carcinoma (HCC) accounts for approximately 80%–90% of all primary liver malignancies. Until 2007, there was no effective treatment option available for patients diagnosed with advanced HCC, whereas today, both multireceptor </span>tyrosine kinase inhibitors as well as </span>immunotherapy combinations have entered clinical practice.</p><p>The choice between the different options is a tailor-made decision to match the efficacy and safety data of the clinical trials with the specific patient and disease profile. This review provides clinical stepstones to make an individualized decision for every patient with its specific tumor and liver characteristics in mind.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977040","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: 1
Highlighting vulnerabilities in the alternative lengthening of telomeres pathway 强调端粒替代延长途径的脆弱性
IF 4 3区 医学
Current Opinion in Pharmacology Pub Date : 2023-06-01 DOI: 10.1016/j.coph.2023.102380
Lisa M. Carson, Rachel L. Flynn
{"title":"Highlighting vulnerabilities in the alternative lengthening of telomeres pathway","authors":"Lisa M. Carson,&nbsp;Rachel L. Flynn","doi":"10.1016/j.coph.2023.102380","DOIUrl":"10.1016/j.coph.2023.102380","url":null,"abstract":"<div><p><span>The alternative lengthening of telomeres (ALT) pathway is a telomere elongation mechanism found in a small but often aggressive subset of cancers. Dependent on break-induced replication, telomere extension in ALT-positive cells relies on a baseline level of </span>DNA replication stress to initiate elongation events. This results in an elevated level of DNA damage and presents a possible vulnerability to be exploited in the development of ALT-targeted cancer therapies. Currently, there are no treatment options that target the ALT mechanism or that are specific for ALT-positive tumors. Here, we review recent developments and promising directions in the development of ALT-targeted therapeutics, many of which involve tipping the balance towards inhibition or exacerbation of ALT activity to selectively target these cells.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9978578","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: 1
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