Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Neurodegener Dis. 2012;10(1-4):212-5. doi: 10.1159/000334536. Epub 2012 Feb 1.
Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by the accumulation and aggregation of misfolded proteins. Disturbed homeostasis in the endoplasmic reticulum leads to accumulation of misfolded proteins, which triggers a stress response called the unfolded protein response (UPR) that protects the cell against the toxic buildup of misfolded proteins.
In this paper, we will briefly review the early involvement of the UPR in the pathology of AD and PD.
Expression of UPR activation markers was analyzed in human brain tissue using immunohistochemistry and Western blot analysis.
Neuropathological studies demonstrate that UPR activation markers are increased in neurons in AD and PD. In AD, UPR activation markers are observed in neurons with diffuse staining of phosphorylated tau protein. In PD, increased immunoreactivity for UPR activation markers is detected in neuromelanin containing dopaminergic neurons of the substantia nigra, which colocalize with diffuse α-synuclein staining.
UPR activation is closely associated with the first stages of accumulation and aggregation of the toxic proteins involved in AD and PD. Studies of postmortem brain tissue indicate that UPR activation is an early event in neurodegeneration.
阿尔茨海默病（AD）和帕金森病（PD）的特征是错误折叠蛋白质的积累和聚集。内质网的稳态失调导致错误折叠蛋白质的积累，从而引发一种被称为未折叠蛋白反应（UPR）的应激反应，该反应可保护细胞免受错误折叠蛋白质的毒性积累。
本文将简要回顾 UPR 在 AD 和 PD 病理中的早期参与。
使用免疫组织化学和 Western blot 分析检测人脑组织中 UPR 激活标志物的表达。
神经病理学研究表明，AD 和 PD 中神经元中 UPR 激活标志物增加。在 AD 中，可见到 UPR 激活标志物在弥漫性磷酸化 tau 蛋白染色的神经元中。在 PD 中，在含有神经黑色素的黑质多巴胺能神经元中检测到 UPR 激活标志物的免疫反应性增加，这些神经元与弥漫性 α-突触核蛋白染色共定位。
UPR 激活与 AD 和 PD 中涉及的毒性蛋白的最初积累和聚集密切相关。对死后脑组织的研究表明，UPR 激活是神经退行性变的早期事件。
