ArticleThe Journal of biological chemistry2011
Proteasomal dysfunction and endoplasmic reticulum stress enhance trafficking of prion protein aggregates through the secretory pathway and increase accumulation of pathologic prion protein.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 59 citations in OpenAlex.
- The protein disulfide isomerase P4HB/PDIA1 modulates cellular and misfolded forms of the prion protein.PLoS pathogens · 2026Article
- Prions and protein aggregates as pathogens, self-propagating structures, biomarkers, and therapeutic targets.Microbiology and molecular biology reviews : MMBR · 2025Review
- Intracellular trafficking SNARE protein, syntaxin-6, modifies prion cellular phenotypes and risk of disease development in vivo.Acta neuropathologica · 2025Article
- TBK1 is a signaling hub in coordinating stress-adaptive mechanisms in head and neck cancer progression.Autophagy · 2025Article
- Preliminary exploration of endoplasmic reticulum stress transmission in astrocytes and neurons, and its mediators.Molecular medicine reports · 2025Article
- A novel ER stress regulator ARL6IP5 induces reticulophagy to ameliorate the prion burden.Autophagy · 2025Article
- Astrocyte in prion disease: a double-edged sword.Neural regeneration research · 2022Review
- Early Aβ42 Exposure Causes Learning Impairment in Later Life.Aging and disease · 2022Article
- The Common Cellular Events in the Neurodegenerative Diseases and the Associated Role of Endoplasmic Reticulum Stress.International journal of molecular sciences · 2022Review
- APP deficiency and HTRA2 modulates PrPBBA advances · 2022Article
- 2,3,5,6-Tetramethylpyrazine protects retinal photoreceptors against endoplasmic reticulum stress by modulating ATF4-mediated inhibition of PRP aggregation.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Prion-Associated Neurodegeneration Causes Both Endoplasmic Reticulum Stress and Proteasome Impairment in a Murine Model of Spontaneous Disease.International journal of molecular sciences · 2021Article
- Endoplasmic Reticulum Stress and Unfolded Protein Response in Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- Sephin1 Reduces Prion Infection in Prion-Infected Cells and Animal Model.Molecular neurobiology · 2020Article
- Proteasomal Inhibition Redirects the PrP-Like Shadoo Protein to the Nucleus.Molecular neurobiology · 2019Article
- Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis.Virologica Sinica · 2019Article
- Overexpression of quality control proteins reduces prion conversion in prion-infected cells.The Journal of biological chemistry · 2018Article
- Interaction of Peptide Aptamers with Prion Protein Central Domain Promotes α-Cleavage of PrPMolecular neurobiology · 2018Article
- XBP1 and PERK Have Distinct Roles in Aβ-Induced Pathology.Molecular neurobiology · 2018Article
- Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis.PLoS pathogens · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A conformational change of the cellular prion protein (PrP(c)) underlies formation of PrP(Sc), which is closely associated with pathogenesis and transmission of prion diseases. The precise conformational prerequisites and the cellular environment necessary for this post-translational process remain to be completely elucidated. At steady state, glycosylated PrP(c) is found primarily at the cell surface, whereas a minor fraction of the population is disposed of by the ER-associated degradation-proteasome pathway. However, chronic ER stress conditions and proteasomal dysfunctions lead to accumulation of aggregation-prone PrP molecules in the cytosol and to neurodegeneration. In this study, we challenged different cell lines by inducing ER stress or inhibiting proteasomal activity and analyzed the subsequent repercussion on PrP metabolism, focusing on PrP in the secretory pathway. Both events led to enhanced detection of PrP aggregates and a significant increase of PrP(Sc) in persistently prion-infected cells, which could be reversed by overexpression of proteins of the cellular quality control. Remarkably, upon proteasomal impairment, an increased fraction of misfolded, fully glycosylated PrP molecules traveled through the secretory pathway and reached the plasma membrane. These findings suggest a novel pathway that possibly provides additional substrate and template necessary for prion formation when protein clearance by the proteasome is impaired.
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