Drug discovery today. Disease mechanisms最新文献_第8页

Regulation of mitochondrial processes: A target for heart failure 线粒体过程的调控:心力衰竭的靶标

Drug discovery today. Disease mechanisms Pub Date : 2010-06-01 DOI: 10.1016/j.ddmec.2010.07.002

Suresh Selvaraj Palaniyandi , Xin Qi , Gouri Yogalingam , Julio Cesar Batista Ferreira , Daria Mochly-Rosen

引用次数: 53

Fixing ryanodine receptor Ca2+ leak – a novel therapeutic strategy for contractile failure in heart and skeletal muscle 固定ryanodine受体Ca2+泄漏-心脏和骨骼肌收缩衰竭的新治疗策略

Drug discovery today. Disease mechanisms Pub Date : 2010-06-01 DOI: 10.1016/j.ddmec.2010.09.009

Daniel C. Andersson , Andrew R. Marks

{"title":"Fixing ryanodine receptor Ca2+ leak – a novel therapeutic strategy for contractile failure in heart and skeletal muscle","authors":"Daniel C. Andersson , Andrew R. Marks","doi":"10.1016/j.ddmec.2010.09.009","DOIUrl":"10.1016/j.ddmec.2010.09.009","url":null,"abstract":"<div>A crucial component in regulating cardiac and skeletal muscles contractility is the release of Ca2+ via ryanodine receptor (RyR) Ca2+ release channels in the sarcoplasmic reticulum (SR). In heart failure and myopathy, the RyR has been found to be excessively phosphorylated or nitrosylated and depleted of the RyR-stabilizing protein calstabin (FK506 binding protein 12/12.6). This remodeling of the RyR channel complex results in an intracellular SR Ca2+ leak and impaired contractility. Despite recent advances in heart failure treatment, there are still devastatingly high mortality rates with this disease. Moreover, pharmacological treatment for muscle weakness and myopathy is nearly nonexistent. A novel class of RyR-stabilizing drugs, rycals, which reduce Ca2+ leak by stabilizing the RyR channels due to preservation of the RyR-calstabin interaction, have recently been shown to improve contractile function in both heart and skeletal muscles. This opens up a novel therapeutic strategy for the treatment of contractile failure in cardiac and skeletal muscle.</div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 2","pages":"Pages e151-e157"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.09.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29497595","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: 79

Targeting G protein-coupled receptor kinases (GRKs) in heart failure G蛋白偶联受体激酶(GRKs)在心力衰竭中的靶向作用

Drug discovery today. Disease mechanisms Pub Date : 2010-06-01 DOI: 10.1016/j.ddmec.2010.07.007

Henriette Brinks , Walter J Koch

引用次数: 23

Diabetic cardiomyopathy: mechanisms and therapeutic targets 糖尿病性心肌病:机制和治疗靶点

Drug discovery today. Disease mechanisms Pub Date : 2010-06-01 DOI: 10.1016/j.ddmec.2010.08.001

Pavan K Battiprolu , Thomas G Gillette , Zhao V Wang , Sergio Lavandero , Joseph A Hill

引用次数: 140

Mechanisms underlying heart failure 心力衰竭的机制

Drug discovery today. Disease mechanisms Pub Date : 2010-06-01 DOI: 10.1016/j.ddmec.2010.10.001

Mark E. Anderson

引用次数: 1

Rethinking resynch: Exploring mechanisms of cardiac resynchronization beyond wall motion control 重新思考再同步:探索超越壁运动控制的心脏再同步机制

Drug discovery today. Disease mechanisms Pub Date : 2010-06-01 DOI: 10.1016/j.ddmec.2010.07.003

Khalid Chakir, David A. Kass

{"title":"Rethinking resynch: Exploring mechanisms of cardiac resynchronization beyond wall motion control","authors":"Khalid Chakir, David A. Kass","doi":"10.1016/j.ddmec.2010.07.003","DOIUrl":"10.1016/j.ddmec.2010.07.003","url":null,"abstract":"<div>Cardiac resynchronization (CRT) is a widely used clinical treatment for heart failure patients with depressed function and discoordinate contraction due to conduction delay. It is unique among heart failure treatments as it both acutely and chronically enhances systolic function and also prolongs survival. While improved chamber mechano-energetics has been considered a primary mechanism for CRT benefit, new animal model data are revealing novel and in many instances unique cellular and molecular modifications from the treatment. Examples of these changes are the reversal of marked regional heterogeneity of the transcriptome and stress kinase signaling, improved ion channel function involved with electrical repolarization, enhanced sarcomere function and calcium handling and up-regulation of beta-adrenergic responses, and improved mitochondrial energetic efficiency associated with targeted changes in the mitochondrial proteome. Exploration of these mechanisms may reveal key insights into how CRT can indeed get the failing heart to contract more and perform more work, yet not worsen long-term failure. These changes may provide a more biological marker for both the appropriate patients for CRT and point the way for new therapeutic avenues for heart failure in general.</div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 2","pages":"Pages e103-e107"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.07.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29635396","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: 7

Developing small molecules to inhibit kinases unkind to the heart: p38 MAPK as a case in point 开发小分子来抑制对心脏不利的激酶:p38 MAPK就是一个很好的例子

Drug discovery today. Disease mechanisms Pub Date : 2010-06-01 DOI: 10.1016/j.ddmec.2010.07.006

Michael S. Marber , Jeffery D. Molkentin , Thomas Force

引用次数: 29

Promises and pitfalls in cell replacement therapy for heart failure 心脏衰竭细胞替代疗法的前景和缺陷

Drug discovery today. Disease mechanisms Pub Date : 2010-06-01 DOI: 10.1016/j.ddmec.2010.07.004

Markus Krane , Oliver Wernet , Sean M. Wu

引用次数: 9

Reprogramming the Mycobacterium tuberculosis transcriptome during pathogenesis 结核分枝杆菌在发病过程中的转录组重编程

Drug discovery today. Disease mechanisms Pub Date : 2010-03-01 DOI: 10.1016/j.ddmec.2010.09.007

Simon J Waddell

引用次数: 4

Does M. tuberculosis genomic diversity explain disease diversity? 结核分枝杆菌基因组多样性能解释疾病多样性吗?

Drug discovery today. Disease mechanisms Pub Date : 2010-03-01 DOI: 10.1016/j.ddmec.2010.09.004

Mireilla Coscolla , Sebastien Gagneux

引用次数: 161