ArticlePloS one2011
Expression of mutant or cytosolic PrP in transgenic mice and cells is not associated with endoplasmic reticulum stress or proteasome dysfunction.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Endoplasmic reticulum stress and ubiquitin-proteasome system impairment in natural scrapie.Frontiers in molecular neuroscience · 2023Article
- Proteostasis unbalance in prion diseases: Mechanisms of neurodegeneration and therapeutic targets.Frontiers in neuroscience · 2022Review
- Prion-Associated Neurodegeneration Causes Both Endoplasmic Reticulum Stress and Proteasome Impairment in a Murine Model of Spontaneous Disease.International journal of molecular sciences · 2021Article
- Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice.Brain : a journal of neurology · 2017Article
- Misfolding leads the way to unraveling signaling pathways in the pathophysiology of prion diseases.Prion · 2016Review
- Activation of the unfolded protein response and granulovacuolar degeneration are not common features of human prion pathology.Acta neuropathologica communications · 2016Article
- Article
- Familial prion protein mutants inhibit Hrd1-mediated retrotranslocation of misfolded proteins by depleting misfolded protein sensor BiP.Human molecular genetics · 2016Article
- The Protein-disulfide Isomerase ERp57 Regulates the Steady-state Levels of the Prion Protein.The Journal of biological chemistry · 2015Article
- The elusive role of the prion protein and the mechanism of toxicity in prion disease.PLoS pathogens · 2015Review
- Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease.PLoS pathogens · 2015Article
- Synaptic dysfunction in prion diseases: a trafficking problem?International journal of cell biology · 2013Review
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- Article
- Misfolded PrP impairs the UPS by interaction with the 20S proteasome and inhibition of substrate entry.The EMBO journal · 2011Article
- Activation of Src family kinase ameliorates secretory trafficking in mutant prion protein cells.The Journal of biological chemistryArticle
- Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The cellular pathways activated by mutant prion protein (PrP) in genetic prion diseases, ultimately leading to neuronal dysfunction and degeneration, are not known. Several mutant PrPs misfold in the early secretory pathway and reside longer in the endoplasmic reticulum (ER) possibly stimulating ER stress-related pathogenic mechanisms. To investigate whether mutant PrP induced maladaptive responses, we checked key elements of the unfolded protein response (UPR) in transgenic mice, primary neurons and transfected cells expressing two different mutant PrPs. Because ER stress favors the formation of untranslocated PrP that might aggregate in the cytosol and impair proteasome function, we also measured the activity of the ubiquitin proteasome system (UPS). Molecular, biochemical and immunohistochemical analyses found no increase in the expression of UPR-regulated genes, such as Grp78/Bip, CHOP/GADD153, or ER stress-dependent splicing of the mRNA encoding the X-box-binding protein 1. No alterations in UPS activity were detected in mutant mouse brains and primary neurons using the Ub(G76V)-GFP reporter and a new fluorogenic peptide for monitoring proteasomal proteolytic activity in vivo. Finally, there was no loss of proteasome function in neurons in which endogenous PrP was forced to accumulate in the cytosol by inhibiting cotranslational translocation. These results indicate that neither ER stress, nor perturbation of proteasome activity plays a major pathogenic role in prion diseases.
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