The heat shock response and small molecule regulators.
The heat shock response and small molecule regulators.
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DOI：
10.1016/j.ejmech.2021.113846
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发表时间：
2021-12-15
影响因子：
6.7
通讯作者：
Blagg BSJ
中科院分区：
文献类型：
--
作者：
Kurop MK;Huyen CM;Kelly JH;Blagg BSJ
热休克反应（HSR）是一种高度保守的细胞途径，负责缓解应激和变性蛋白质的重折叠。当宿主细胞暴露于热休克、缺血或有毒物质等条件时，热休克因子-1 (HSF-1)（一种转录因子）会激活编码热休克蛋白 (Hsps) 的基因，热休克蛋白是一个蛋白质家族，与其他分子伴侣一起发挥作用，缓解压力并重新折叠已变性的蛋白质。随着变性蛋白质的重折叠，热休克蛋白将错误折叠的蛋白质护送至降解途径，从而促进错误折叠蛋白质的去除，从而防止错误折叠的蛋白质积累。研究表明，许多病理状况，如糖尿病、癌症、神经病、心血管疾病和衰老都会对 HSR 功能产生负面影响，并且通常与错误折叠的蛋白质聚集有关。研究表明线粒体稳态和 HSF-1 水平之间的相互作用可以影响应激抵抗、蛋白质稳态和恶性细胞生长，这进一步支持了 Hsps 在病理和代谢功能中的作用。另一方面，特定小分子激活热休克蛋白可以诱导热休克反应，从而提供神经保护和其他益处。本综述将重点关注 Hsp 和 HSR 的调节作为治疗这些疾病的治疗选择。
The heat shock response (HSR) is a highly conserved cellular pathway that is responsible for stress relief and the refolding of denatured proteins. When a host cell is exposed to conditions such as heat shock, ischemia, or toxic substances, heat shock factor- 1 (HSF- 1), a transcription factor, activates the genes that encode for the heat shock proteins (Hsps), which are a family of proteins that work alongside other chaperones to relieve stress and refold proteins that have been denatured. Along with the refolding of denatured proteins, Hsps facilitate the removal of misfolded proteins by escorting them to degradation pathways, thereby preventing the accumulation of misfolded proteins. Research has indicated that many pathological conditions, such as diabetes, cancer, neuropathy, cardiovascular disease, and aging have a negative impact on HSR function and are commonly associated with misfolded protein aggregation,. Studies indicate an interplay between mitochondrial homeostasis and HSF-1 levels can impact stress resistance, proteostasis, and malignant cell growth, which further support the role of Hsps in pathological and metabolic functions. On the other hand, Hsp activation by specific small molecules can induce the heat shock response, which can afford neuroprotection and other benefits. This review will focus on the modulation of Hsps and the HSR as therapeutic options to treat these conditions.
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影响因子：
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作者：
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