Molecular Chaperone ORP150 in ER Stress-related Diseases
Molecular Chaperone ORP150 in ER Stress-related Diseases
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DOI：
10.2174/1381612811319150016
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发表时间：
2013-05-01
影响因子：
3.1
通讯作者：
Cechowska-Pasko, Marzanna
中科院分区：
文献类型：
--
作者：
Kusaczuk, Magdalena;Cechowska-Pasko, Marzanna
内质网（ER）正常功能的许多干扰导致未折叠蛋白质在ER腔内积聚，触发进化保守反应，称为未折叠蛋白反应（UPR）。UPR是使细胞能够科普在细胞暴露于各种不利条件后在ER腔中积累的未折叠蛋白质的机制。UPR过程具有强烈的促生存作用，但当压力变得严重且无法解决时，则会转向凋亡性细胞死亡。UPR的细胞保护分支的标志是刺激ER分子伴侣的表达，其中ORP 150已经获得了大量的关注。ORP 150已被鉴定为在许多疾病的病理学中过表达，并且参与对环境应激的细胞应答。虽然已经提出了一些关于ORP 150分子活性的零碎结果，但其确切的作用模式仍然不清楚。本文重点阐述了ORP150在糖尿病、神经退行性疾病、心血管疾病和癌症等主要内质网应激相关疾病发病机制中的作用。
Many disturbances in the normal function of endoplasmic reticulum (ER) cause accumulation of unfolded proteins in the lumen of ER, triggering an evolutionary conserved response, termed the unfolded protein response (UPR). The UPR is the mechanism enabling cells to cope with unfolded proteins, accumulated in ER lumen after the cell has been exposed to various unfavorable conditions. The UPR process has strong prosurvival implications, but switches towards apoptotic cell death when the stress becomes severe and unsolvable. The hallmark of the cytoprotective branch of UPR is stimulation of the expression of ER chaperones, of which ORP150 has gained a great deal of attention. ORP150 has been identified as being overexpressed in the pathology of many diseases and is involved in the cellular response to environmental stress. Although some fragmentary results concerning ORP150 molecular activity have been presented, its exact mode of action still remains unclear. In this paper we focused on the role of ORP150 in the pathogenesis of the main types of ER stress-related diseases: diabetes, neurodegenerative diseases, cardiovascular diseases and cancer.