ArticleCell death & disease2011
Human PrP90-231-induced cell death is associated with intracellular accumulation of insoluble and protease-resistant macroaggregates and lysosomal dysfunction.
Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Article
- Proteostasis unbalance in prion diseases: Mechanisms of neurodegeneration and therapeutic targets.Frontiers in neuroscience · 2022Review
- RNA-seq and network analysis reveal unique glial gene expression signatures during prion infection.Molecular brain · 2020Article
- Emerging Role of Cellular Prion Protein in the Maintenance and Expansion of Glioma Stem Cells.Cells · 2019Review
- Effects of Prion Protein on Aβ42 and Pyroglutamate-Modified AβpΕ3-42 Oligomerization and Toxicity.Molecular neurobiology · 2019Article
- Autophagy Activator Drugs: A New Opportunity in Neuroprotection from Misfolded Protein Toxicity.International journal of molecular sciences · 2019Review
- Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death.Cell death & disease · 2018Article
- Different Molecular Mechanisms Mediate Direct or Glia-Dependent Prion Protein Fragment 90-231 Neurotoxic Effects in Cerebellar Granule Neurons.Neurotoxicity research · 2017Article
- Different Effects of Human Umbilical Cord Mesenchymal Stem Cells on Glioblastoma Stem Cells by Direct Cell Interaction or Via Released Soluble Factors.Frontiers in cellular neuroscience · 2017Article
- Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells.Oncotarget · 2016Article
- Celecoxib Inhibits Prion Protein 90-231-Mediated Pro-inflammatory Responses in Microglial Cells.Molecular neurobiology · 2016Article
- Unfolded Protein Response and Macroautophagy in Alzheimer's, Parkinson's and Prion Diseases.Molecules (Basel, Switzerland) · 2015Review
- Redox control of protein degradation.Redox biology · 2015Review
- A computationally designed DNA aptamer template with specific binding to phosphatidylserine.Nucleic acid therapeutics · 2013Article
- Probing early misfolding events in prion protein mutants by NMR spectroscopy.Molecules (Basel, Switzerland) · 2013Review
- Excitotoxicity through NMDA receptors mediates cerebellar granule neuron apoptosis induced by prion protein 90-231 fragment.Neurotoxicity research · 2013Article
- An intronic ncRNA-dependent regulation of SORL1 expression affecting Aβ formation is upregulated in post-mortem Alzheimer's disease brain samples.Disease models & mechanisms · 2013Article
- Analysis of apoptosis methods recently used in Cancer Research and Cell Death & Disease publications.Cell death & disease · 2012Article
- Calcium binding promotes prion protein fragment 90-231 conformational change toward a membrane destabilizing and cytotoxic structure.PloS one · 2012Article
- A novel collection of snRNA-like promoters with tissue-specific transcription properties.International journal of molecular sciences · 2012Article
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Authors and funding
7 authors.
Funding
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Abstract
To define the mechanisms by which hPrP90-231 induces cell death, we analyzed its interaction with living cells and monitored its intracellular fate. Treatment of SH-SY5Y cells with fluorescein-5-isothiocyanate (FITC)-conjugated hPrP90-231 caused the accumulation of cytosolic aggregates of the prion protein fragment that increased in number and size in a time-dependent manner. The formation of large intracellular hPrP90-231 aggregates correlated with the activation of apoptosis. hPrP90-231 aggregates occurred within lysotracker-positive vesicles and induced the formation of activated cathepsin D (CD), indicating that hPrP90-231 is partitioned into the endosomal-lysosomal system structures, activating the proteolytic machinery. Remarkably, the inhibition of CD activity significantly reduced hPrP-90-231-dependent apoptosis. Internalized hPrP90-231 forms detergent-insoluble and SDS-stable aggregates, displaying partial resistance to proteolysis. By confocal microscopy analysis of lucifer yellow (LY) intracellular partition, we show that hPrP90-231 accumulation induces lysosome destabilization and loss of lysosomal membrane impermeability. In fact, although control cells evidenced a vesicular pattern of LY fluorescence (index of healthy lysosomes), hPrP90-231-treated cells showed diffuse cytosolic fluorescence, indicating LY diffusion through damaged lysosomes. In conclusion, these data indicate that exogenously added hPrP90-231 forms intralysosomal deposits having features of insoluble, protease-resistant aggregates and could trigger a lysosome-mediated apoptosis by inducing lysosome membrane permeabilization, followed by the release of hydrolytic enzymes.
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