ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Manganese upregulates cellular prion protein and contributes to altered stabilization and proteolysis: relevance to role of metals in pathogenesis of prion disease.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Consequences of Disturbing Manganese Homeostasis.International journal of molecular sciences · 2023Review
- Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools.Pharmaceutics · 2023Review
- The manifold role of octapeptide repeats in prion protein assembly.Peptide science (Hoboken, N.J.) · 2023Article
- Impact of Environmental Risk Factors on Mitochondrial Dysfunction, Neuroinflammation, Protein Misfolding, and Oxidative Stress in the Etiopathogenesis of Parkinson's Disease.International journal of molecular sciences · 2022Review
- Manganese-induced neurodegenerative diseases and possible therapeutic approaches.Expert review of neurotherapeutics · 2020Review
- Amyloids: Regulators of Metal Homeostasis in the Synapse.Molecules (Basel, Switzerland) · 2020Review
- Exosomes as Mediators of Chemical-Induced Toxicity.Current environmental health reports · 2019Review
- Manganese-Induced Neurotoxicity: New Insights Into the Triad of Protein Misfolding, Mitochondrial Impairment, and Neuroinflammation.Frontiers in neuroscience · 2019Review
- Manganese exposure induces neuroinflammation by impairing mitochondrial dynamics in astrocytes.Neurotoxicology · 2018Article
- Article
- Exosomes in Toxicology: Relevance to Chemical Exposure and Pathogenesis of Environmentally Linked Diseases.Toxicological sciences : an official journal of the Society of Toxicology · 2017Review
- Integrated Organotypic Slice Cultures and RT-QuIC (OSCAR) Assay: Implications for Translational Discovery in Protein Misfolding Diseases.Scientific reports · 2017Article
- Dietary magnesium and copper affect survival time and neuroinflammation in chronic wasting disease.Prion · 2016Article
- Untangling the Manganese-α-Synuclein Web.Frontiers in neuroscience · 2016Review
- Metals and Neurodegeneration.F1000Research · 2016Review
- Prion (PrPC) expression in ovine uteroplacental tissues increases after estrogen treatment of ovariectomized ewes and during early pregnancy.Reproduction (Cambridge, England) · 2014Article
- Article
- Up-regulation of mRNA ventricular PRNP prion protein gene expression in air pollution highly exposed young urbanites: endoplasmic reticulum stress, glucose regulated protein 78, and nanosized particles.International journal of molecular sciences · 2013Article
- The impact of environmental metals in young urbanites' brains.Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie · 2013Article
- Effect of divalent metals on the neuronal proteasomal system, prion protein ubiquitination and aggregation.Toxicology letters · 2012Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Prion diseases are fatal neurodegenerative diseases resulting from misfolding of normal cellular prion (PrP(C)) into an abnormal form of scrapie prion (PrP(Sc)). The cellular mechanisms underlying the misfolding of PrP(C) are not well understood. Since cellular prion proteins harbor divalent metal-binding sites in the N-terminal region, we examined the effect of manganese on PrP(C) processing in in vitro models of prion disease. Exposure to manganese significantly increased PrP(C) levels both in cytosolic and in membrane-rich fractions in a time-dependent manner. Manganese-induced PrP(C) upregulation was independent of messenger RNA transcription or stability. Additionally, manganese treatment did not alter the PrP(C) degradation by either proteasomal or lysosomal pathways. Interestingly, pulse-chase analysis showed that the PrP(C) turnover rate was significantly altered with manganese treatment, indicating increased stability of PrP(C) with the metal exposure. Limited proteolysis studies with proteinase-K further supported that manganese increases the stability of PrP(C). Incubation of mouse brain slice cultures with manganese also resulted in increased prion protein levels and higher intracellular manganese accumulation. Furthermore, exposure of manganese to an infectious prion cell model, mouse Rocky Mountain Laboratory-infected CAD5 cells, significantly increased prion protein levels. Collectively, our results demonstrate for the first time that divalent metal manganese can alter the stability of prion proteins and suggest that manganese-induced stabilization of prion protein may play a role in prion protein misfolding and prion disease pathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.