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Rho Kinases in Health and Disease: From Basic Science to Translational Research

机译:健康和疾病中的Rho激酶:从基础科学到转化研究

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摘要

Rho-associated kinases ROCK1 and ROCK2 are key regulators of actin cytoskeleton dynamics downstream of Rho GTPases that participate in the control of important physiologic functions, S including cell contraction, migration, proliferation, adhesion, and inflammation. Several excellent review articles dealing with ROCK function and regulation have been published over the past few years. Although a brief overview of general molecular, biochemical, and functional properties of ROCKs is included, an effort has been made to produce an original work by collecting and synthesizing recent studies aimed at translating basic discoveries from cell and experimental models into knowledge of human physiology, pathophysiological mechanisms, and medical therapeutics. This review points out the specificity and distinct roles of ROCK1 and ROCK2 isoforms highlighted in the last few years. Results obtained from genetically modified mice and genetic analysis in humans are discussed. This review also addresses the involvement of ROCKs in human diseases and the potential use of ROCK activity as a biomarker or a pharmacological target for specific inhibitors.
机译:Rho相关激酶ROCK1和ROCK2是Rho GTPases下游肌动蛋白细胞骨架动力学的关键调节因子,参与重要的生理功能(包括细胞的收缩,迁移,增殖,粘附和炎症)的控制。在过去的几年中,发表了一些有关ROCK功能和调节的优秀评论文章。尽管包括了ROCK的一般分子,生化和功能特性的简要概述,但我们已通过收集和综合旨在将细胞和实验模型的基本发现转化为人类生理学知识的最新研究来做出原创作品,病理生理机制和药物治疗。这篇综述指出了最近几年突出的ROCK1和ROCK2同工型的特异性和独特作用。讨论了从转基因小鼠获得的结果和人类的遗传分析。这篇综述还讨论了ROCKs在人类疾病中的参与以及ROCK活性作为特定抑制剂的生物标志物或药理学靶标的潜在用途。

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