ArticleThe Journal of biological chemistry2010
A novel, drug-based, cellular assay for the activity of neurotoxic mutants of the prion protein.
Article in The Journal of biological chemistry, 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, 38 citations in OpenAlex.
- Abnormal synaptic architecture in iPSC-derived neurons from a multi-generational family with genetic Creutzfeldt-Jakob disease.Stem cell reports · 2024Article
- Sigma Receptor Ligands Are Potent Antiprion Compounds that Act Independently of Sigma Receptor Binding.ACS chemical neuroscience · 2024Article
- Mechanisms of prion-induced toxicity.Cell and tissue research · 2023Review
- Intrinsic toxicity of the cellular prion protein is regulated by its conserved central region.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Identification of anti-prion drugs and targets using toxicity-based assays.Current opinion in pharmacology · 2019Review
- An antipsychotic drug exerts anti-prion effects by altering the localization of the cellular prion protein.PloS one · 2017Article
- Identification of Anti-prion Compounds using a Novel Cellular Assay.The Journal of biological chemistry · 2016Article
- The prion protein family member Shadoo induces spontaneous ionic currents in cultured cells.Scientific reports · 2016Article
- A cationic tetrapyrrole inhibits toxic activities of the cellular prion protein.Scientific reports · 2016Article
- Expression of the Prion Protein Family Member Shadoo Causes Drug Hypersensitivity That Is Diminished by the Coexpression of the Wild Type Prion Protein.The Journal of biological chemistry · 2016Article
- Activation of zebrafish Src family kinases by the prion protein is an amyloid-β-sensitive signal that prevents the endocytosis and degradation of E-cadherin/β-catenin complexes in vivo.Molecular neurodegeneration · 2016Article
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- A mutant prion protein sensitizes neurons to glutamate-induced excitotoxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- The heat shock response is modulated by and interferes with toxic effects of scrapie prion protein and amyloid β.The Journal of biological chemistry · 2012Article
- Prion protein at the crossroads of physiology and disease.Trends in neurosciences · 2012Review
- Prion pathogenesis is faithfully reproduced in cerebellar organotypic slice cultures.PLoS pathogens · 2012Article
- The toxicity of a mutant prion protein is cell-autonomous, and can be suppressed by wild-type prion protein on adjacent cells.PloS one · 2012Article
- Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication.Virology journal · 2011Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
In prion diseases, the infectious isoform of the prion protein (PrP(Sc)) may subvert a normal, physiological activity of the cellular isoform (PrP(C)). A deletion mutant of the prion protein (Delta105-125) that produces a neonatal lethal phenotype when expressed in transgenic mice provides a window into the normal function of PrP(C) and how it can be corrupted to produce neurotoxic effects. We report here the surprising and unexpected observation that cells expressing Delta105-125 PrP and related mutants are hypersensitive to the toxic effects of two classes of antibiotics (aminoglycosides and bleomycin analogues) that are commonly used for selection of stably transfected cell lines. This unusual phenomenon mimics several essential features of Delta105-125 PrP toxicity seen in transgenic mice, including rescue by co-expression of wild type PrP. Cells expressing Delta105-125 PrP are susceptible to drug toxicity within minutes, suggesting that the mutant protein enhances cellular accumulation of these cationic compounds. Our results establish a screenable cellular phenotype for the activity of neurotoxic forms of PrP, and they suggest possible mechanisms by which these molecules could produce their pathological effects in vivo.
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Registered trials
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.