Molecular Chaperone Accumulation in Cancer and Decrease in Alzheimer's Disease: The Potential Roles of HSF1.
Molecular Chaperone Accumulation in Cancer and Decrease in Alzheimer's Disease: The Potential Roles of HSF1.
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DOI：
10.3389/fnins.2017.00192
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发表时间：
2017
影响因子：
4.3
通讯作者：
Murshid A
中科院分区：
文献类型：
--
作者：
Calderwood SK;Murshid A
分子伴侣是维持蛋白质组折叠和功能状态所必需的。当细胞内折叠的挑战发生时，热休克反应被触发，导致一类被称为热休克蛋白（HSP）的诱导型分子伴侣的合成增加。尽管已知大多数细胞的HSP合成会随着衰老而普遍下降，但在一些与高龄相关的疾病中，这一过程的程度差异相当显着。在阿尔茨海默病（AD）中，一种普遍存在于大脑中的蛋白质折叠障碍，一些关键类别的神经元的热休克反应变得降低。HSP表达的下降可能是细胞生理学的许多方面随着年龄的增长和/或对AD中特别观察到的代谢病理变化的反应而普遍减弱的结果。与正常衰老细胞相反，癌细胞经历HSP水平的从头增加。HSP表达的这种扩展归因于癌症中折叠需求的增加或在快速适应的癌细胞中诱导热休克反应的新机制的进化。由于HSP合成调控的主要途径涉及转录因子HSF 1，因此已表明该因子的失调可能在每种疾病的发展中起决定性作用。我们将讨论什么是已知的机制HSF 1的调节方面的HSP失调中看到的AD和癌症。
Molecular chaperones are required to maintain the proteome in a folded and functional state. When challenges to intracellular folding occur, the heat shock response is triggered, leading to increased synthesis of a class of inducible chaperones known as heat shock proteins (HSP). Although HSP synthesis is known to undergo a general decline in most cells with aging, the extent of this process varies quite markedly in some of the diseases associated with advanced age. In Alzheimer's disease (AD), a prevalent protein folding disorder in the brain, the heat shock response of some critical classes of neurons becomes reduced. The resulting decline in HSP expression may be a consequence of the general enfeeblement of many aspects of cell physiology with aging and/or a response to the pathological changes in metabolism observed specifically in AD. Cancer cells, in contrast to normal aging cells, undergo de novo increases in HSP levels. This expansion in HSP expression has been attributed to increases in folding demand in cancer or to the evolution of new mechanisms for induction of the heat shock response in rapidly adapting cancer cells. As the predominant pathway for regulation of HSP synthesis involves transcription factor HSF1, it has been suggested that dysregulation of this factor may play a decisive role in the development of each disease. We will discuss what is known of the mechanisms of HSF1 regulation in regard to the HSP dysregulation seen in in AD and cancer.