Crosstalk Between Endoplasmic Reticulum Stress, Oxidative Stress, and Autophagy: Potential Therapeutic Targets for Acute CNS Injuries.
Crosstalk Between Endoplasmic Reticulum Stress, Oxidative Stress, and Autophagy: Potential Therapeutic Targets for Acute CNS Injuries.
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DOI：
10.1007/s12035-014-9029-6
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发表时间：
2016-01
影响因子：
5.1
通讯作者：
Vemuganti, Raghu
中科院分区：
文献类型：
--
作者：
Nakka, Venkata Prasuja;Prakash-babu, Phanithi;Vemuganti, Raghu
内质网应激可诱导多种神经细胞死亡途径，在卒中的病理生理过程中发挥重要作用。当未折叠/错误折叠的蛋白质积累，并且内质网伴侣蛋白的折叠能力超过内质网管腔促进其处置的能力时，就会发生内质网应激。因此，将诱导一系列复杂的信号通路从内质网传递到胞浆和胞核，以补偿损伤并恢复正常的细胞内稳态，统称为未折叠蛋白反应(UPR)。然而，由于严重或长期的应激，UPR失败会导致细胞死亡。在急性中枢神经系统损伤后，蛋白质折叠的慢性障碍和氧化应激延长了内质网应激，导致持续的内质网功能障碍和神经细胞死亡。虽然中风后的内质网应激反应已经被很好地研究了，但仍有必要研究内质网应激与其他细胞通路之间的联系，这些通路会加剧损伤后神经元的死亡。在这篇综述中，我们总结了内质网应激在急性脑损伤中的作用，强调了与内质网应激相关的不同的分子机制，以及它与氧化应激和自噬的关系。我们还讨论了旨在减少内质网应激以保护急性损伤后中枢神经系统的现有和正在开发的治疗方案。
Endoplasmic reticulum (ER) stress induces a variety of neuronal cell death pathways that play a critical role in the pathophysiology of Stroke. ER stress occurs when unfolded/misfolded proteins accumulate and the folding capacity of ER chaperones exceeds the capacity of ER lumen to facilitate their disposal. As a consequence, a complex set of signaling pathways will be induced that transmit from ER to cytosol and nucleus to compensate damage and to restore the normal cellular homeostasis, collectively known as unfolded protein response (UPR). However, failure of UPR due to severe or prolonged stress leads to cell death. Following acute CNS injuries, chronic disturbances in protein folding and oxidative stress prolong ER stress leading to sustained ER dysfunction and neuronal cell death. While ER stress responses have been well studied after stroke, there is an emerging need to study the association of ER stress with other cell pathways that exacerbate neuronal death after an injury. In this review we summarize the current understanding of the role for ER stress in acute brain injuries, highlighting the diverse molecular mechanisms associated with ER stress and its relation to oxidative stress and autophagy. We also discussed the existing and developing therapeutic options aimed to reduce ER stress to protect the CNS after acute injuries.
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DOI：
10.1093/jnen/62.4.329
发表时间：
2003-04-01
影响因子：
3.2
作者：
Ferrer, I;Planas, AM
通讯作者：
Planas, AM
影响因子：
4
作者：
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影响因子：
64.8
作者：
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Ron, D
影响因子：
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作者：
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通讯作者：
Takahashi, Ryosuke
影响因子：
10.6
作者：
Boland, Barry;Nixon, Ralph A.
通讯作者：
Nixon, Ralph A.