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应激诱导反应与热休克蛋白:细胞保护的新药理学靶点

Stress-inducible responses and heat shock proteins: new pharmacologic targets for cytoprotection.

作者信息

Morimoto R I, Santoro M G

机构信息

Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.

出版信息

Nat Biotechnol. 1998 Sep;16(9):833-8. doi: 10.1038/nbt0998-833.

Abstract

Molecular chaperones protect proteins against environmental and physiologic stress and from the deleterious consequences of an imbalance in protein homeostasis. Many of these stresses, if prolonged, result in defective development and pathologies associated with a diverse array of diseases due to tissue injury and repair including stroke, myocardial reperfusion damage, ischemia, cancer, amyloidosis, and other neurodegenerative diseases. We discuss the molecular nature of the stress signals, the mechanisms that underlie activation of the heat shock response, the role of heat shock proteins as cytoprotective molecules, and strategies for pharmacologically active molecules as regulators of the heat shock response.

摘要

分子伴侣可保护蛋白质免受环境和生理应激的影响,以及防止蛋白质稳态失衡带来的有害后果。如果这些应激状态持续时间过长,会导致发育缺陷以及与多种疾病相关的病理状况,这些疾病包括由于组织损伤和修复引起的中风、心肌再灌注损伤、局部缺血、癌症、淀粉样变性以及其他神经退行性疾病。我们将讨论应激信号的分子本质、热休克反应激活的潜在机制、热休克蛋白作为细胞保护分子的作用,以及作为热休克反应调节剂的药理活性分子策略。

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