Protein folding stress in neurodegenerative diseases: a glimpse into the ER
Protein folding stress in neurodegenerative diseases: a glimpse into the ER
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DOI：
10.1016/j.ceb.2011.01.003
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发表时间：
2011-04-01
影响因子：
7.5
通讯作者：
Hetz, Claudio
中科院分区：
文献类型：
--
作者：
Matus, Soledad;Glimcher, Laurie H.;Hetz, Claudio
几种神经退行性疾病具有共同的神经病理学，主要特征是脑中存在含有特定错误折叠蛋白的异常蛋白质内含物。最近的证据表明，细胞器功能的改变是蛋白质错误折叠疾病的常见病理特征，突出了内质网（ER）稳态的扰动。ER应激的迹象已经在大多数神经系统疾病的实验模型中检测到，最近在患有神经退行性疾病的人类患者的大脑样本中检测到。为了科普ER应激，细胞激活称为未折叠蛋白质反应（UPR）的整合信号传导反应，其目的是部分通过调节参与蛋白质折叠、质量控制和降解途径的基因来重建稳态。在这里，我们讨论了目前提出的特定机制，参与在不同的神经退行性疾病的蛋白质折叠应力的产生，并推测可能的治疗干预。
Several neurodegenerative diseases share common neuropathology, primarily featuring the presence in the brain of abnormal protein inclusions containing specific misfolded proteins. Recent evidence indicates that alteration in organelle function is a common pathological feature of protein misfolding disorders, highlighting perturbations in the homeostasis of the endoplasmic reticulum (ER). Signs of ER stress have been detected in most experimental models of neurological disorders and more recently in brain samples from human patients with neurodegenerative disease. To cope with ER stress, cells activate an integrated signaling response termed the unfolded protein response (UPR), which aims to reestablish homeostasis in part through regulation of genes involved in protein folding, quality control and degradation pathways. Here we discuss the particular mechanisms currently proposed to be involved in the generation of protein folding stress in different neurodegenerative conditions and speculate about possible therapeutic interventions.