Drug discovery today. Disease mechanisms最新文献

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Carnitine homeostasis, mitochondrial function and cardiovascular disease 肉毒碱稳态、线粒体功能和心血管疾病
Drug discovery today. Disease mechanisms Pub Date : 2009-01-01 DOI: 10.1016/j.ddmec.2009.02.001
Shruti Sharma, Stephen M. Black
{"title":"Carnitine homeostasis, mitochondrial function and cardiovascular disease","authors":"Shruti Sharma,&nbsp;Stephen M. Black","doi":"10.1016/j.ddmec.2009.02.001","DOIUrl":"10.1016/j.ddmec.2009.02.001","url":null,"abstract":"<div><p><span><span><span>Carnitines are involved in mitochondrial transport of fatty acids and are of critical importance for maintaining normal mitochondrial function. This review summarizes recent experimental and clinical studies showing that mitochondrial dysfunction secondary to a disruption of carnitine </span>homeostasis may play a role in decreased </span>NO<span> signaling and the development of endothelial dysfunction. Future challenges include development of agents that can positively modulate </span></span><span>l</span>-carnitine homeostasis which may have high therapeutic potential.</p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"6 1","pages":"Pages e31-e39"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2009.02.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29136036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 137
The role of the estrogen receptors in obesity 雌激素受体在肥胖中的作用
Drug discovery today. Disease mechanisms Pub Date : 2009-01-01 DOI: 10.1016/j.ddmec.2009.11.001
Tatiana V. Kramarova, Karin Dahlman Wright, Ingemar Pongratz
{"title":"The role of the estrogen receptors in obesity","authors":"Tatiana V. Kramarova,&nbsp;Karin Dahlman Wright,&nbsp;Ingemar Pongratz","doi":"10.1016/j.ddmec.2009.11.001","DOIUrl":"10.1016/j.ddmec.2009.11.001","url":null,"abstract":"<div><p><span>The incidence of obesity in the modern society has reached epidemic proportions and constitutes a great public health concern. Epidemiological, retrospective and genetic studies have linked estrogens to obesity and body mass distribution. This review aims to provide a general overview regarding the role of the </span>estrogen receptors for the development of obesity at the molecular level.</p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"6 1","pages":"Pages e49-e54"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2009.11.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89326458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Hepatitis C virus proteins promote mitochondrial bioenergetic dysfunction and nitro-oxidative stress: insights into pathogenesis 丙型肝炎病毒蛋白促进线粒体生物能量功能障碍和氮氧化应激:对发病机制的见解
Drug discovery today. Disease mechanisms Pub Date : 2009-01-01 DOI: 10.1016/j.ddmec.2008.12.001
N. Capitanio , D. Moradpour , C. Piccoli
{"title":"Hepatitis C virus proteins promote mitochondrial bioenergetic dysfunction and nitro-oxidative stress: insights into pathogenesis","authors":"N. Capitanio ,&nbsp;D. Moradpour ,&nbsp;C. Piccoli","doi":"10.1016/j.ddmec.2008.12.001","DOIUrl":"10.1016/j.ddmec.2008.12.001","url":null,"abstract":"<div><p><span>HCV-infection induces a state of oxidative stress<span> more pronounced than in many other inflammatory diseases. Here we propose a temporal sequence of events in the HCV-infected cell whereby the primary alteration consists in release of Ca</span></span><sup>2+</sup><span> from the ER followed by uptake into mitochondria. This triggers successive mitochondrial dysfunctions leading to generation of ROS and to a progressive metabolic adaptive response. Pathogenetic implications of the model and new opportunities for therapeutic intervention are discussed.</span></p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"6 1","pages":"Pages e3-e10"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2008.12.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72389465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Role of mitochondria in liver pathophysiology 线粒体在肝脏病理生理中的作用
Drug discovery today. Disease mechanisms Pub Date : 2009-01-01 DOI: 10.1016/j.ddmec.2010.05.003
Shunhei Yamashina, Nobuhiro Sato, Kazuyoshi Kon, Kenichi Ikejima, Sumio Watanabe
{"title":"Role of mitochondria in liver pathophysiology","authors":"Shunhei Yamashina,&nbsp;Nobuhiro Sato,&nbsp;Kazuyoshi Kon,&nbsp;Kenichi Ikejima,&nbsp;Sumio Watanabe","doi":"10.1016/j.ddmec.2010.05.003","DOIUrl":"10.1016/j.ddmec.2010.05.003","url":null,"abstract":"<div><p><span>Mitochondria play a central role in cellular energy homeostasis, metabolism, and cell death. Mitochondria generate energy via the </span>electron transport chain<span><span><span> located in the inner membrane for the synthesis of ATP. In the mitochondrial respiratory pathway, leakage of electrons induces the production of </span>reactive oxygen species involved in the cellular aging and DNA damage. It is suggested that </span>liver carcinogenesis<span>, chronic hepatitis C<span>, alcoholic liver disease and non-alcoholic fatty liver disease are the result of reactive oxygen species production because of mitochondrial dysfunction. The advancement of therapeutic approaches to protect mitochondria heralds a new strategy to halt progressive liver diseases and carcinogenesis.</span></span></span></p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"6 1","pages":"Pages e25-e30"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.05.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77228467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
NR4A orphan nuclear receptors in cardiovascular biology NR4A孤儿核受体在心血管生物学中的应用
Drug discovery today. Disease mechanisms Pub Date : 2009-01-01 DOI: 10.1016/j.ddmec.2009.06.001
Yue Zhao, Dennis Bruemmer
{"title":"NR4A orphan nuclear receptors in cardiovascular biology","authors":"Yue Zhao,&nbsp;Dennis Bruemmer","doi":"10.1016/j.ddmec.2009.06.001","DOIUrl":"10.1016/j.ddmec.2009.06.001","url":null,"abstract":"<div><p>The NR4A orphan nuclear receptor<span> subfamily comprises the highly homologous receptors Nur77<span><span><span> (NR4A1), Nurr1 (NR4A2) and NOR1<span><span> (NR4A3). These evolutionarily conserved and ancient receptors function as ligand-independent transcription factors that regulate the expression of overlapping target genes. As early response genes, the basal expression level of these receptors is low but rapidly induced as a result of the changes in environmental cues. The transcriptional activity of these receptors is primarily regulated by gene induction and </span>posttranslational modifications of the receptor including phosphorylation. NR4A receptors were initially identified in the brain and early functional studies suggested a role for these receptors in signal- and cell-specific stimulation of both apoptosis and proliferation. More recent studies have revealed much broader functions of these </span></span>orphan receptors including the regulation of genes involved in cancer, metabolism, energy balance, </span>atherosclerosis<span> and vascular remodeling<span><span>. In this review, we will discuss our current understanding of the molecular biology of NR4A receptors and summarize recent studies suggesting an important role of these orphan receptors in </span>vascular biology.</span></span></span></span></p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"6 1","pages":"Pages e43-e48"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2009.06.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29136040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 30
Contents page. 内容页面。
Drug discovery today. Disease mechanisms Pub Date : 2009-01-01 DOI: 10.1016/S1740-6765(10)00006-4
{"title":"Contents page.","authors":"","doi":"10.1016/S1740-6765(10)00006-4","DOIUrl":"https://doi.org/10.1016/S1740-6765(10)00006-4","url":null,"abstract":"","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"6 1","pages":"Page i"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1740-6765(10)00006-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138187021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial dysfunction in nonalcoholic steatohepatitis (NASH): are there drugs able to improve it? 非酒精性脂肪性肝炎(NASH)的线粒体功能障碍:有药物可以改善它吗?
Drug discovery today. Disease mechanisms Pub Date : 2009-01-01 DOI: 10.1016/j.ddmec.2009.02.002
Karima Begriche , Laetitia Knockaert , Julie Massart , Marie-Anne Robin , Bernard Fromenty
{"title":"Mitochondrial dysfunction in nonalcoholic steatohepatitis (NASH): are there drugs able to improve it?","authors":"Karima Begriche ,&nbsp;Laetitia Knockaert ,&nbsp;Julie Massart ,&nbsp;Marie-Anne Robin ,&nbsp;Bernard Fromenty","doi":"10.1016/j.ddmec.2009.02.002","DOIUrl":"10.1016/j.ddmec.2009.02.002","url":null,"abstract":"<div><p><span><span><span>Calorie-enriched diet and lack of work out are causing a worldwide surge of obesity and insulin resistance (IR), which favors lipid accretion in the liver (i.e. </span>hepatic steatosis<span>, or fatty liver). Indeed, IR in the adipose tissue increases lipolysis and the entry of </span></span>free fatty acids<span> (FFAs) in the liver, whereas IR-associated hyperinsulinemia favors </span></span><em>de novo</em><span><span><span><span> synthesis of FFAs and triacylglycerol (TAG) molecules (i.e. lipogenesis). Fortunately, some hormonal and metabolic adaptations are set up to restrain </span>fat accumulation<span><span><span> in the liver, such as an increase in fatty acid oxidation (FAO). Although fatty liver is a benign condition in majority of patients, it can develop in some individuals into </span>nonalcoholic steatohepatitis (NASH), which can further evolve into </span>cirrhosis<span>. Currently, the mechanisms responsible for this progression are still poorly understood but could involve the overproduction of reactive oxygen species<span> (ROS) and a large array of deleterious cytokines that promote cell death, inflammation and fibrosis. Importantly, mitochondria appear to be a major site of ROS generation within the hepatocytes during NASH, which could be related to lower </span></span></span></span>glutathione<span> (GSH) import in these organelles, increased local expression of cytochrome P450 2E1 (CYP2E1) and enhanced leakage of electrons from the mitochondrial </span></span>respiratory chain (MRC) caused by boosted FAO and concomitant MRC impairment. A vicious circle can ensue because ROS can damage the mitochondrial DNA and key components of the MRC, thus further impairing the MRC and augmenting electron leakage and ROS formation. In theory, the ideal drug for the treatment of NASH would reduce fat accretion in the liver and decrease cytokine and ROS overproduction. Although this drug does not exist at the moment, there are some synthetic and natural derivatives presenting metabolic and/or antioxidative effects that can directly or indirectly improve mitochondrial function during NASH.</span></p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"6 1","pages":"Pages e11-e23"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2009.02.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83825131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
Targeting nuclear receptors in cardiometabolic disease 在心脏代谢疾病中靶向核受体
Drug discovery today. Disease mechanisms Pub Date : 2009-01-01 DOI: 10.1016/j.ddmec.2010.05.001
Ulrich Kintscher
{"title":"Targeting nuclear receptors in cardiometabolic disease","authors":"Ulrich Kintscher","doi":"10.1016/j.ddmec.2010.05.001","DOIUrl":"10.1016/j.ddmec.2010.05.001","url":null,"abstract":"","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"6 1","pages":"Pages 41-42"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.05.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74727652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
How to modulate FXR activity to treat the Metabolic Syndrome 如何调节FXR活性治疗代谢综合征
Drug discovery today. Disease mechanisms Pub Date : 2009-01-01 DOI: 10.1016/j.ddmec.2010.05.002
Janne Prawitt , Sandrine Caron , Bart Staels
{"title":"How to modulate FXR activity to treat the Metabolic Syndrome","authors":"Janne Prawitt ,&nbsp;Sandrine Caron ,&nbsp;Bart Staels","doi":"10.1016/j.ddmec.2010.05.002","DOIUrl":"10.1016/j.ddmec.2010.05.002","url":null,"abstract":"<div><p><span>The Metabolic Syndrome<span> (MS) represents a public health problem which takes epidemic proportions worldwide. In addition to life-style interventions the development of effective therapies for the MS and its complications such as cardiovascular disease (CVD) and type 2 diabetes<span> (T2D) is a major challenge of the future decades. The nuclear receptor<span> farnesoid X receptor (FXR) is a potential pharmacological target, because of its broad spectrum of functions and the possibility of modulating its activity in a gene-specific manner by the so-called selective </span></span></span></span>bile acid receptor modulators (SBARM). This review will discuss the numerous regulatory functions of FXR that overlap with components of the MS and the potential benefit of modulating FXR activity for MS therapy.</p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"6 1","pages":"Pages e55-e64"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.05.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79855661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
G-protein-mediated signalling in salt-dependent hypertension 盐依赖性高血压中g蛋白介导的信号传导
Drug discovery today. Disease mechanisms Pub Date : 2008-12-01 DOI: 10.1016/j.ddmec.2008.09.003
Angela Wirth, Stefan Offermanns
{"title":"G-protein-mediated signalling in salt-dependent hypertension","authors":"Angela Wirth,&nbsp;Stefan Offermanns","doi":"10.1016/j.ddmec.2008.09.003","DOIUrl":"10.1016/j.ddmec.2008.09.003","url":null,"abstract":"<div><p>Arterial hypertension is a common health problem which represents a major risk factor for a variety of diseases like myocardial infarction or stroke. An environmental factor that still attracts a lot of interest in this context is the dietary intake of salt (sodium chloride). Multiple evidence indicates that an increased salt intake increases the risk for hypertension. The precise mechanisms linking high salt intake to high blood pressure are still unclear. This review summarises data on G-protein-coupled receptors and their downstream signalling pathways<span> in vascular smooth muscle cells implicated in the pathophysiology of salt-dependent hypertension.</span></p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"5 3","pages":"Pages e307-e314"},"PeriodicalIF":0.0,"publicationDate":"2008-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2008.09.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83624298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
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