Cellular prion protein modulates β-amyloid deposition in aged APP/PS1 transgenic mice

Ordóñez-Gutiérrez, Lara; Torres, Juan María; Gavı́n, Rosalina; Antón, Marta; Arroba, Ana I.; Espinosa, Juan-Carlos; Vergara, Cristina; Rı́o, José Antonio del

doi:10.1016/j.neurobiolaging.2013.05.019

Cited by 17 publications

(16 citation statements)

References 62 publications

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“…In addition, we also observed increased PrP C in Tg20-derived cultures after ADDL treatment which may also contribute to the increased levels of ptau (tyr 18 ) observed in our previous study [69] and the study by Larson et al in 14-month-old mice [41]. However, we were unable to determine differences in ptau epitopes (other than tyr 18 ) in old APP/PS1 mice with different PrP C dosages, although we did demonstrate an increase in tau levels in APP/PS1 mice lacking PrP C with respect to APP/PS1-Prnp +/+ as also reported by Larson et al [41].…”

Section: Prp C Expression Addls Tau Phosphorylation and Neuroprotecsupporting

confidence: 77%

“…Along these lines, we recently reported increased phosphorylation levels of tyr 18 in older (~ 9 months) but not younger (3-6 months) APP/PS1 mice overexpressing PrP C [69]. The data presented more recently by…”

Section: Prp C Expression Addls Tau Phosphorylation and Neuroprotecmentioning

confidence: 71%

“…Triple APP/PS1/Prnp 0/0 Tg mice [69] showed a ~22% increased expression of tau at 9 months of age compared with non-Tg APP/PS1/Prnp 0/0 mice (Fig. 3a,b), in contrast to APP/PS1 expressing normal levels of PrP C with the same tau levels (data not shown).…”

Section: Parallel Progression Of Prp C and Tau Expression In App/ps1 mentioning

confidence: 85%

“…In fact, PrP C seems not to play a crucial role in survival in Parkinson, taupathies, or APP/PS1 mouse models [79,69]. Although tau phosphorylation was not analyzed, no differences were observed in the tangle levels in the brain parenchyma of P301L mice with different Prnp dosages [79].…”

Section: Discussionmentioning

confidence: 96%

“…Several studies have analyzed the putative role of PrP C expression in the survival of various models of neurodegenerative diseases (e.g., [79,69]. In fact, PrP C seems not to play a crucial role in survival in Parkinson, taupathies, or APP/PS1 mouse models [79,69].…”

Section: Discussionmentioning

confidence: 99%

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Role of PrPC Expression in Tau Protein Levels and Phosphorylation in Alzheimer’s Disease Evolution

et al. 2014

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Alzheimer's disease (AD) is characterized by the presence of amyloid plaques mainly consisting of hydrophobic -amyloid peptide (A) aggregates and neurofibrillary tangles (NFTs) composed principally of hyperphosphorylated tau. A oligomers have been described as the earliest effectors to negatively affect synaptic structure and plasticity in the affected brains, and cellular prion protein (PrP C ) has been proposed as receptor for these oligomers.The most widely accepted theory holds that the toxic effects of A are upstream of change in tau, a neuronal microtubule-associated protein that promotes the polymerization and stabilization of microtubules. However, tau is considered decisive for the progression of neurodegeneration, and indeed tau pathology correlates well with clinical symptoms such as dementia. Different pathways can lead to abnormal phosphorylation, and, as a consequence, tau aggregates into Paired Helical Filaments (PHF) and later on into NFTs.Reported data suggest a regulatory tendency of PrP C expression in the development of AD, and a putative relationship between PrP C and tau processing is emerging. However the role of tau/PrP C interaction in AD is poorly understood.In this study we show increased susceptibility to A derived diffusible ligands (ADDLs) in neuronal primary cultures from PrP C knock-out mice, compared to wild-type, which correlates with increased tau expression. Moreover, we found increased PrP C expression that paralleled with tau at early ages in an AD murine model, and in early Braak stages of AD in affected individuals. Taken together, these results suggest a protective role for PrP C in AD by down-regulating tau expression, and they point to this protein as being crucial in the molecular events that lead to neurodegeneration in AD.

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Section: Prp C Expression Addls Tau Phosphorylation and Neuroprotecsupporting

confidence: 77%

Section: Prp C Expression Addls Tau Phosphorylation and Neuroprotecmentioning

confidence: 71%

Section: Parallel Progression Of Prp C and Tau Expression In App/ps1 mentioning

confidence: 85%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Role of PrPC Expression in Tau Protein Levels and Phosphorylation in Alzheimer’s Disease Evolution

et al. 2014

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Aβ-induced acceleration of Alzheimer-related τ-pathology spreading and its association with prion protein

et al. 2019

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Creutzfeldt-Jakob Disease Subtype-Specific Regional and Temporal Regulation of ADP Ribosylation Factor-1-Dependent Rho/MLC Pathway at Pre-Clinical Stage

et al. 2015

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Small GTPases of the Arf family mainly activate the formation of coated carrier vesicles. We showed that class-I Arf1 interacts specifically with full length GPI-anchored cellular prion protein (PrP(C)). Several recent reports have also demonstrated a missing link between the endoplasmic reticulum and the Golgi-complex role for proper folding, but the exact molecular mechanism is not yet fully understood. In the present study, we identified and characterized the interactive role of Arf1 during PrP(C) intracellular distribution under pathophysiological conditions. PrP(C) interaction with Arf1 was investigated in cortical primary neuronal cultures of PrP(C) wild type and knockout mice (PrP(-/-)). Arf1 and PrP(C) co-binding affinity was confirmed using reverse co-immunoprecipitation, co-localization affinity using confocal laser-scanning microscopy. Treatment with brefeldin-A modulated Arf1 expression and resulted in down-regulation and redistribution of PrP(C) into cytosolic region. In the pre-symptomatic stage of the disease, Arf1 expression was significantly downregulated in the frontal cortex in tg340 mice expressing about fourfold of human PrP-M129 with PrP null background that had been inoculated with human sCJD MM1 brain tissue homogenates (sCJD MM1 mice). In addition, the frontal cortex of CJD human brain demonstrated significant binding capacity of Arf1 protein using co-immunoprecipitation analysis. We also examined Arf1 expression in the brain of CJD patients with the subtypes MM1 and VV2 and found that it was regulated in a region-specific manner. In the frontal cortex, Arf1 expression was not significantly changed in either MM1 or VV2 subtype. Interestingly, Arf1 expression was significantly reduced in the cerebellum in both subtypes as compared to controls. Furthermore, we observed altered RhoA activity, which in turn affects myosin light-chain (MLC) phosphorylation and Arf1-dependent PI3K pathway. Together, our findings underscore a key early symptomatic role of Arf1 in neurodegeneration. Targeting the Arf/Rho/MLC signaling axis might be a promising strategy to uncover the missing link which probably influences disease progression and internal homeostasis of misfolded proteins.

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Cellular prion protein modulates β-amyloid deposition in aged APP/PS1 transgenic mice

Cited by 17 publications

References 62 publications

Role of PrPC Expression in Tau Protein Levels and Phosphorylation in Alzheimer’s Disease Evolution

Role of PrPC Expression in Tau Protein Levels and Phosphorylation in Alzheimer’s Disease Evolution

Aβ-induced acceleration of Alzheimer-related τ-pathology spreading and its association with prion protein

Creutzfeldt-Jakob Disease Subtype-Specific Regional and Temporal Regulation of ADP Ribosylation Factor-1-Dependent Rho/MLC Pathway at Pre-Clinical Stage

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