Department of Genome Analysis and Department of Neurology; Academic Medical Center; University of Amsterdam; Amsterdam, The Netherlands.
Autophagy. 2011 Aug;7(8):910-1. doi: 10.4161/auto.7.8.15761. Epub 2011 Aug 1.
Protein folding stress in the endoplasmic reticulum (ER) may lead to activation of the unfolded protein response (UPR), aimed to restore proteostasis in the ER. Previously, we demonstrated that UPR activation is an early event in Alzheimer disease (AD) brain. In our recent work we investigated whether activation of the UPR is employed to enhance the capacity of the ubiquitin proteasome system or autophagy in neuronal cells. We showed that the levels, composition and activity of the proteasome are not regulated by the UPR. In contrast, UPR activation enhances autophagy and LC3 levels are increased in neurons displaying UPR activation in AD brain. Our data suggest that autophagy is the major degradational pathway following UPR activation in neuronal cells and indicate a connection between UPR activation and autophagic pathology in AD brain.
内质网中的蛋白质折叠应激可能导致未折叠蛋白反应 (UPR) 的激活，其目的是恢复内质网中的蛋白质平衡。此前，我们证明了 UPR 的激活是阿尔茨海默病 (AD) 大脑中的早期事件。在我们最近的工作中，我们研究了 UPR 的激活是否被用来增强神经元细胞中泛素蛋白酶体系统或自噬的能力。我们表明，蛋白酶体的水平、组成和活性不受 UPR 的调节。相反，UPR 的激活增强了自噬，并且在 AD 大脑中显示 UPR 激活的神经元中 LC3 水平增加。我们的数据表明，自噬是神经元细胞中 UPR 激活后的主要降解途径，并表明 UPR 激活与 AD 大脑中的自噬病理学之间存在联系。
