Whitehouse Isobel J, Brown Deborah, Baybutt Herbert, Diack Abigail B, Kellett Katherine A B, Piccardo Pedro, Manson Jean C, Hooper Nigel M
School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, United Kingdom.
PLoS One. 2016 Jul 22;11(7):e0159119. doi: 10.1371/journal.pone.0159119. eCollection 2016.
The cellular prion protein (PrPC) has been proposed to play an important role in the pathogenesis of Alzheimer's disease. In cellular models PrPC inhibited the action of the β-secretase BACE1 on wild type amyloid precursor protein resulting in a reduction in amyloid-β (Aβ) peptides. Here we have assessed the effect of genetic ablation of PrPC in transgenic mice expressing human wild type amyloid precursor protein (line I5). Deletion of PrPC had no effect on the α- and β-secretase proteolysis of the amyloid precursor protein (APP) nor on the amount of Aβ38, Aβ40 or Aβ42 in the brains of the mice. In addition, ablation of PrPC did not alter Aβ deposition or histopathology phenotype in this transgenic model. Thus using this transgenic model we could not provide evidence to support the hypothesis that PrPC regulates Aβ production.
细胞朊蛋白（PrPC）被认为在阿尔茨海默病的发病机制中起重要作用。在细胞模型中，PrPC抑制β-分泌酶BACE1对野生型淀粉样前体蛋白的作用，从而导致淀粉样β（Aβ）肽减少。在此，我们评估了在表达人类野生型淀粉样前体蛋白的转基因小鼠（I5系）中PrPC基因缺失的影响。PrPC的缺失对淀粉样前体蛋白（APP）的α-和β-分泌酶蛋白水解没有影响，对小鼠大脑中Aβ38、Aβ40或Aβ42的量也没有影响。此外，在这个转基因模型中，PrPC的缺失并没有改变Aβ沉积或组织病理学表型。因此，使用这个转基因模型，我们无法提供证据支持PrPC调节Aβ产生这一假说。
