未折叠蛋白反应
内质网
神经退行性变
细胞生物学
蛋白激酶R
肌萎缩侧索硬化
生物
蛋白激酶A
程序性细胞死亡
ATF6
激酶
医学
神经科学
细胞凋亡
疾病
内科学
丝裂原活化蛋白激酶激酶
遗传学
作者
Chunchen Xiang,Yujia Wang,Han Zhang,Fang Han
出处
期刊:Apoptosis
[Springer Nature]
日期:2016-11-04
卷期号:22 (1): 1-26
被引量:171
标识
DOI:10.1007/s10495-016-1296-4
摘要
The endoplasmic reticulum (ER) is an important organelle involved in cellular homeostasis and control of protein quality. Unfolded protein response (UPR) is a cellular response to ER stress and promotes cell survival. Severe or prolonged stress activates apoptosis signaling to trigger cell death. In mammals, the UPR is initiated by three major ER stress sensors, including inositol-requiring transmembrane kinase 1, double-stranded RNA-activated protein kinase-like ER kinase and activating transcription factor 6. UPR dysfunction plays an important role in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease, which is characterized by the accumulation and aggregation of misfolded proteins. ER stress mediates the pathogenesis of psychiatric diseases, such as depression, schizophrenia, sleep fragmentation and post-traumatic stress disorder. The role of UPR in the neuropathology of humans, cell lines and animal models, is established. Therefore, inhibition of specific ER mediators may contribute to the treatment and prevention of neurodegeneration. Preclinical studies have shed light on the potential therapeutic strategies. Here, we will review the evidence of UPR activation in neurodegenerative disorders and psychiatric diseases along with the methodology.
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