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Impact of the cellular prion protein on amyloid-β and 3PO-tau processing.
- Source :
-
Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2014; Vol. 38 (3), pp. 551-65. - Publication Year :
- 2014
-
Abstract
- Previous studies indicate an important role for the cellular prion protein (PrP(C)) in the development of Alzheimer's disease (AD) pathology. In the present study, we analyzed the involvement of PrP(C) in different pathological mechanisms underlying AD: the processing of the amyloid-β protein precursor (AβPP) and its interaction with AβPP, tau, and different phosphorylated forms of the tau protein (p-tau). The effect of PrP(C) on tau expression was investigated in various cellular compartments using a HEK293 cell model expressing a tau mutant (3PO-tau) or wild type (WT)-tau. We could show that PrP(C) reduces AβPP cleavage, leading to decreased levels of Aβ40 and sAβPP without changing the protein expression of AβPP, β-secretase, or γ-secretase. Tau and its phosphorylated forms were identified as interactions partners for PrP(C), raising the question as to whether PrP(C) might also be involved in tau pathology. Overexpression of PrP(C) in PRNP and 3PO-tau transfected cells resulted in a reduction of 3PO-tau and p-tau as well as a decrease of 3PO-tau-related toxicity. In addition, we used the transgenic PrP(C) knockout (Prnp0/0) mouse line to study the dynamics of tau phosphorylation, an important pathological hallmark in the pathogenesis of AD in vivo. There, an effect of PrP(C) on tau expression could be observed under oxidative stress conditions but not during aging. In summary, we provide further evidence for interactions of PrP(C) with proteins that are known to be the key players in AD pathogenesis. We identified tau and its phosphorylated forms as potential PrP-interactors and report a novel protective function of PrP(C) in AD-like tau pathology.
- Subjects :
- Amyloid Precursor Protein Secretases metabolism
Amyloid beta-Protein Precursor metabolism
Animals
Brain blood supply
Brain metabolism
Cell Line
Disease Models, Animal
HEK293 Cells
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neuroblastoma pathology
Amyloid beta-Peptides metabolism
Gene Expression Regulation genetics
Mutation genetics
Prions metabolism
tau Proteins genetics
tau Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1875-8908
- Volume :
- 38
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of Alzheimer's disease : JAD
- Publication Type :
- Academic Journal
- Accession number :
- 24028865
- Full Text :
- https://doi.org/10.3233/JAD-130566