Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype.
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 hav...
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0159119&type=printable |
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| author | Isobel J Whitehouse Deborah Brown Herbert Baybutt Abigail B Diack Katherine A B Kellett Pedro Piccardo Jean C Manson Nigel M Hooper |
| author_facet | Isobel J Whitehouse Deborah Brown Herbert Baybutt Abigail B Diack Katherine A B Kellett Pedro Piccardo Jean C Manson Nigel M Hooper |
| author_sort | Isobel J Whitehouse |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-661eb766a5da451a8aa047e01b1089fe |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-661eb766a5da451a8aa047e01b1089fe2025-08-20T02:03:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01117e015911910.1371/journal.pone.0159119Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype.Isobel J WhitehouseDeborah BrownHerbert BaybuttAbigail B DiackKatherine A B KellettPedro PiccardoJean C MansonNigel M HooperThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0159119&type=printable |
| spellingShingle | Isobel J Whitehouse Deborah Brown Herbert Baybutt Abigail B Diack Katherine A B Kellett Pedro Piccardo Jean C Manson Nigel M Hooper Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype. PLoS ONE |
| title | Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype. |
| title_full | Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype. |
| title_fullStr | Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype. |
| title_full_unstemmed | Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype. |
| title_short | Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype. |
| title_sort | ablation of prion protein in wild type human amyloid precursor protein app transgenic mice does not alter the proteolysis of app levels of amyloid β or pathologic phenotype |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0159119&type=printable |
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