Cellular stress/the unfolded protein response: relevance to sleep and sleep disorders.
Cellular stress/the unfolded protein response: relevance to sleep and sleep disorders.
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DOI：
10.1016/j.smrv.2009.01.001
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发表时间：
2009-06
影响因子：
10.5
通讯作者：
Naidoo, Nirinjini
中科院分区：
文献类型：
--
作者：
Naidoo, Nirinjini
关键词：
最近的转录分析和微阵列研究开始揭开睡眠的一些奥秘。最重要的线索之一是鉴定了内质网常驻伴侣 BiP，在所有研究的物种中，BiP 都会随着睡眠剥夺而增加。 BiP 是一种 ER 常驻伴侣，是称为 ER 应激反应或未折叠蛋白反应的信号通路的关键细胞标记物和主要调节因子。 The ER stress response occurs in 3 phases.当内质网压力适中时，它是健康的、具有保护性的和适应性的。适应性反应的失败会导致炎症反应的激活。当内质网应激负担巨大且持续时间较长时，刽子手通路就会被激活。总的来说，这项工作提供了新的证据，证明适度的睡眠剥夺会诱发细胞应激，从而激活适应性反应。衰老会使人们对睡眠剥夺的反应从适应性和保护性的反应转向适应不良的反应。了解睡眠不足激活的途径及其发生机制将有助于开发在长时间清醒期间保护大脑的疗法，特别是在睡眠障碍（包括与衰老相关的睡眠障碍）中。
Recent transcript profiling and microarray studies are beginning to unveil some of the mysteries of sleep. One of the most important clues has been the identification of the ER resident chaperone, BiP that increases with sleep deprivation in all species studied. BiP, an ER resident chaperone is the key cellular marker and master regulator of a signaling pathway called the ER stress response or unfolded protein response. The ER stress response occurs in 3 phases. It is healthy, protective and adaptive when the ER stress is moderate. Failure of the adaptive response leads to the activation of an inflammatory response. When the ER stress burden is great and prolonged, executioner pathways are activated. Collectively this work provides new evidence that modest sleep deprivation induces cellular stress that activates an adaptive response. Aging tilts the response to sleep deprivation from one that is adaptive and protective to one that is maladaptive. Understanding the pathways activated by sleep loss and the mechanisms by which they occur will allow the development of therapies to protect the brain during prolonged wakefulness and specifically in sleep disorders including those associated with aging.
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