Endoplasmic reticulum stress response and neurodegeneration
Endoplasmic reticulum stress response and neurodegeneration
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DOI：
10.1016/j.ceca.2005.06.019
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发表时间：
2005-09-01
期刊：
影响因子：
4
通讯作者：
Mengesdorf, T
中科院分区：
文献类型：
--
作者：
Paschen, W;Mengesdorf, T
内质网（ER）是一个亚细胞区室，在钙储存和信号传导中起着核心作用。内质网钙稳态紊乱是一种严重的应激形式，干扰了内质网结构的核心功能，包括新合成膜和分泌蛋白的折叠和加工。阻断折叠和加工反应会导致未折叠蛋白质的积累，形成潜在的毒性聚集体。为了恢复内质网功能，特定的应激反应被激活，其中一种是未折叠蛋白反应（UPR）。UPR的特点是关闭全局蛋白质合成和激活编码er驻留蛋白的基因表达，这些蛋白参与折叠和加工反应。因此，内质网钙稳态不可避免地与主要的细胞功能相关，包括基因转录和翻译。内质网钙稳态和内质网功能被认为在各种大脑退行性疾病中受损，包括阿尔茨海默病、帕金森病和亨廷顿病，以及肌萎缩侧索硬化症。内质网功能也被证明在脑缺血和创伤等急性病理状态下受到干扰，这已被确定为退行性疾病发展的危险因素。这意味着存在共同的潜在病理机制。这篇综述将总结新的观察结果，表明内质网功能的损害可能是导致大脑急性疾病和退行性疾病中神经元细胞损伤的病理过程的共同特征。(C) 2005 Elsevier Ltd版权所有。
The endoplasmic reticulum (ER) is a subcellular compartment playing a central role in calcium storage and signaling. Disturbances of ER calcium homeostasis constitute a severe form of stress interfering with central functions of this structure including the folding and processing of newly synthesized membrane and secretory proteins. Blocking the folding and processing reactions results in the accumulation of unfolded proteins forming potentially toxic aggregates. To restore ER functioning, specific stress responses are activated one of which is the unfolded protein response (UPR). UPR is characterized by a shutdown of global protein synthesis and activation of expression of genes coding for ER-resident proteins that are involved in the folding and processing reactions. ER calcium homeostasis is therefore inevitably associated with major cellular functions, including gene transcription and translation. ER calcium homeostasis und ER functions are believed to be impaired in various degenerative diseases of the brain including Alzheimer's, Parkinson's and Huntington's disease, and amyotrophic lateral sclerosis. ER functioning has also been shown to be disturbed in acute pathological states of the brain such as ischemia and trauma, which have been identified as risk factors for the development of degenerative diseases. This implies that there are common underlying pathomechanisms. This review will summarize new observations suggesting that impairment of ER functioning may be a common denominator of pathological processes resulting in neuronal cell injury in acute disorders and degenerative diseases of the brain. (C) 2005 Elsevier Ltd. All rights reserved.