在具有阿尔茨海默病样神经病理学特征的转基因小鼠大脑皮层中,β-淀粉样蛋白降解酶IDE的表达增加。

Increased expression of Abeta degrading enzyme IDE in the cortex of transgenic mice with Alzheimer's disease-like neuropathology.

作者信息

Vepsäläinen Saila, Hiltunen Mikko, Helisalmi Seppo, Wang Jun, van Groen Thomas, Tanila Heikki, Soininen Hilkka

机构信息

Department of Neurology, University Hospital and University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland.

出版信息

Neurosci Lett. 2008 Jun 20;438(2):216-20. doi: 10.1016/j.neulet.2008.04.025. Epub 2008 Apr 12.

Abstract

Expression levels of amyloid beta (Abeta)-degrading enzymes, insulin degrading enzyme (IDE) and neprilysin (NEP), were examined in transgenic mice with Alzheimer's disease-like neuropathology. After the development of first Abeta plaques in transgenic mice brain, cortical mRNA and protein levels of IDE were significantly up-regulated in the transgenic mice compared to their non-transgenic littermates. Up-regulation of IDE mRNA-levels occurred in parallel with increased Abeta40 and Abeta42 production. Additionally, a significant positive correlation was observed between protein levels of IDE and full-length amyloid precursor protein (APP) in the cerebral cortex. mRNA and protein levels of NEP were also nominally up-regulated in Tg mice compared to controls. These data may reflect up-regulation of the IDE and possibly of NEP expression in response to the Abeta accumulation.

摘要

在具有阿尔茨海默病样神经病理学特征的转基因小鼠中,检测了β淀粉样蛋白(Aβ)降解酶、胰岛素降解酶(IDE)和中性内肽酶(NEP)的表达水平。在转基因小鼠大脑中首次出现Aβ斑块后,与非转基因同窝小鼠相比,转基因小鼠皮质中IDE的mRNA和蛋白质水平显著上调。IDE mRNA水平的上调与Aβ40和Aβ42产量的增加同时发生。此外,在大脑皮质中观察到IDE蛋白水平与全长淀粉样前体蛋白(APP)之间存在显著正相关。与对照组相比,Tg小鼠中NEP的mRNA和蛋白质水平也有轻微上调。这些数据可能反映了IDE以及可能还有NEP表达上调以应对Aβ积累。

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