Proteotoxicity: an underappreciated pathology in cardiac disease.
Proteotoxicity: an underappreciated pathology in cardiac disease.
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DOI：
10.1016/j.yjmcc.2013.12.015
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发表时间：
2014-06
影响因子：
5
通讯作者：
Robbins, Jeffrey
中科院分区：
文献类型：
--
作者：
Sandri, Marco;Robbins, Jeffrey
一般而言，在大多数器官系统中，细胞内蛋白质稳态是许多因素的总和，包括染色体状态、蛋白质合成、翻译后加工和转运、折叠、组装和拆卸成大分子复合物、蛋白质稳定性和清除。在心脏中，人们一直专注于在致病过程中激活的基因程序，但受损蛋白质和细胞器的去除在心脏病的发病机制中发挥着重要作用。蛋白质毒性是指受损或错误折叠的蛋白质甚至细胞器对细胞的不利影响。在细胞水平，不受控制或严重蛋白毒性的最终结果是细胞死亡;因此，蛋白毒性的致病影响最大程度地表现在没有再生能力或再生能力非常差的器官中，如大脑和心脏。心脏蛋白毒性增加的证据在先天性和获得性人类心脏病的大子集中迅速增加。在动物模型和细胞培养中进行的研究已经开始确立蛋白毒性作为心脏主要致病因素的充分性和必要性。这就要求严格测试蛋白毒性衰减作为治疗心脏病的新策略的功效。这篇综述文章强调了我们对错误折叠蛋白质如何在细胞中损伤和处理的理解的一些最新进展，研究了靶向蛋白毒性作为心脏病新治疗策略的新证据。
In general, in most organ systems, intracellular protein homeostasis is the sum of many factors, including chromosomal state, protein synthesis, post-translational processing and transport, folding, assembly and disassembly into macromolecular complexes, protein stability and clearance. In the heart, there has been a focus on the gene programs that are activated during pathogenic processes, but the removal of damaged proteins and organelles has been underappreciated as playing an important role in the pathogenesis of heart disease. Proteotoxicity refers to the adverse effects of damaged or misfolded proteins and even organelles on the cell. At the cellular level, the ultimate outcome of uncontrolled or severe proteotoxicity is cell death; hence, the pathogenic impact of proteotoxicity is maximally manifested in organs with no or very poor regenerative capability such as the brain and the heart. Evidence for increased cardiac proteotoxicity is rapidly mounting for a large subset of congenital and acquired human heart disease. Studies carried out in animal models and in cell culture have begun to establish both sufficiency and, in some cases, the necessity of proteotoxicity as a major pathogenic factor in the heart. This dictates rigorous testing for the efficacy of proteotoxic attenuation as a new strategy to treat heart disease. This review article highlights some recent advances in our understanding of how misfolded proteins can injure and are handled in the cell, examining the emerging evidence for targeting proteotoxicity as a new therapeutic strategy for heart disease.
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DOI：
10.1016/j.biocel.2012.06.006
发表时间：
2012-10
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Christians ES;Ishiwata T;Benjamin IJ
通讯作者：
Benjamin IJ
影响因子：
3.6
作者：
Dimitrakis, Polychronis;Romay-Ogando, Maria-Iris;Zuppinger, Christian
通讯作者：
Zuppinger, Christian
影响因子：
4
作者：
Chen, Yongqiang;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.
影响因子：
3.3
作者：
Cridge, Belinda J;Rosengren, Rhonda J
通讯作者：
Rosengren, Rhonda J
影响因子：
13.3
作者：
Dunlop, Elaine A.;Hunt, David K.;Tee, Andrew R.
通讯作者：
Tee, Andrew R.