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• W2913356574 abstract "Prion diseases are untreatable and invariably fatal, making the discovery of effective therapeutic interventions a priority. Most candidate molecules have been discovered based on their ability to reduce the levels of PrPSc, the infectious form of the prion protein, in cultured neuroblastoma cells. We have employed an alternative assay, based on an abnormal cellular phenotype associated with a mutant prion protein, to discover a novel class of anti-prion compounds, the phenethyl piperidines. Using an assay that monitors the acute toxic effects of PrPSc on the synapses of cultured hippocampal neurons, we have identified p38 MAPK as a druggable pharmacological target that is already being pursued for the treatment of other human diseases. Organotypic brain slices, which can propagate prions and mimic several neuropathological features of the disease, have also been used to test inhibitory compounds. An effective anti-prion regimen will involve synergistic combination of drugs acting at multiple steps of the pathogenic process, resulting not only in reduction in prion levels but also suppression of neurotoxic signaling." @default.
• W2913356574 created "2019-02-21" @default.
• W2913356574 creator A5032728621 @default.
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• W2913356574 date "2019-02-01" @default.
• W2913356574 modified "2023-10-18" @default.
• W2913356574 title "Identification of anti-prion drugs and targets using toxicity-based assays" @default.
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• W2913356574 doi "https://doi.org/10.1016/j.coph.2018.12.005" @default.
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