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Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons

Prion diseases are caused by PrP(Sc), a self-replicating pathologically misfolded protein that exerts toxicity predominantly in the brain. The administration of PrP(Sc) causes a robust, reproducible and specific disease manifestation. Here, we have applied a combination of translating ribosome affin...

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Autores principales: Scheckel, Claudia, Imeri, Marigona, Schwarz, Petra, Aguzzi, Adriano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527237/
https://www.ncbi.nlm.nih.gov/pubmed/32960170
http://dx.doi.org/10.7554/eLife.62911
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author Scheckel, Claudia
Imeri, Marigona
Schwarz, Petra
Aguzzi, Adriano
author_facet Scheckel, Claudia
Imeri, Marigona
Schwarz, Petra
Aguzzi, Adriano
author_sort Scheckel, Claudia
collection PubMed
description Prion diseases are caused by PrP(Sc), a self-replicating pathologically misfolded protein that exerts toxicity predominantly in the brain. The administration of PrP(Sc) causes a robust, reproducible and specific disease manifestation. Here, we have applied a combination of translating ribosome affinity purification and ribosome profiling to identify biologically relevant prion-induced changes during disease progression in a cell-type-specific and genome-wide manner. Terminally diseased mice with severe neurological symptoms showed extensive alterations in astrocytes and microglia. Surprisingly, we detected only minor changes in the translational profiles of neurons. Prion-induced alterations in glia overlapped with those identified in other neurodegenerative diseases, suggesting that similar events occur in a broad spectrum of pathologies. Our results suggest that aberrant translation within glia may suffice to cause severe neurological symptoms and may even be the primary driver of prion disease.
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spelling pubmed-75272372020-10-01 Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons Scheckel, Claudia Imeri, Marigona Schwarz, Petra Aguzzi, Adriano eLife Neuroscience Prion diseases are caused by PrP(Sc), a self-replicating pathologically misfolded protein that exerts toxicity predominantly in the brain. The administration of PrP(Sc) causes a robust, reproducible and specific disease manifestation. Here, we have applied a combination of translating ribosome affinity purification and ribosome profiling to identify biologically relevant prion-induced changes during disease progression in a cell-type-specific and genome-wide manner. Terminally diseased mice with severe neurological symptoms showed extensive alterations in astrocytes and microglia. Surprisingly, we detected only minor changes in the translational profiles of neurons. Prion-induced alterations in glia overlapped with those identified in other neurodegenerative diseases, suggesting that similar events occur in a broad spectrum of pathologies. Our results suggest that aberrant translation within glia may suffice to cause severe neurological symptoms and may even be the primary driver of prion disease. eLife Sciences Publications, Ltd 2020-09-22 /pmc/articles/PMC7527237/ /pubmed/32960170 http://dx.doi.org/10.7554/eLife.62911 Text en © 2020, Scheckel et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Scheckel, Claudia
Imeri, Marigona
Schwarz, Petra
Aguzzi, Adriano
Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons
title Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons
title_full Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons
title_fullStr Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons
title_full_unstemmed Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons
title_short Ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons
title_sort ribosomal profiling during prion disease uncovers progressive translational derangement in glia but not in neurons
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527237/
https://www.ncbi.nlm.nih.gov/pubmed/32960170
http://dx.doi.org/10.7554/eLife.62911
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