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Prions: Generation and Spread Versus Neurotoxicity

Neurodegenerative diseases are characterized by the aggregation of misfolded proteins in the brain. Among these disorders are the prion diseases, which are transmissible, and in which the misfolded proteins (“prions”) are also the infectious agent. Increasingly, it appears that misfolded proteins in...

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Detalles Bibliográficos
Autores principales: Halliday, Mark, Radford, Helois, Mallucci, Giovanna R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106307/
https://www.ncbi.nlm.nih.gov/pubmed/24860100
http://dx.doi.org/10.1074/jbc.R114.568477
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author Halliday, Mark
Radford, Helois
Mallucci, Giovanna R.
author_facet Halliday, Mark
Radford, Helois
Mallucci, Giovanna R.
author_sort Halliday, Mark
collection PubMed
description Neurodegenerative diseases are characterized by the aggregation of misfolded proteins in the brain. Among these disorders are the prion diseases, which are transmissible, and in which the misfolded proteins (“prions”) are also the infectious agent. Increasingly, it appears that misfolded proteins in Alzheimer and Parkinson diseases and the tauopathies also propagate in a “prion-like” manner. However, the association between prion formation, spread, and neurotoxicity is not clear. Recently, we showed that in prion disease, protein misfolding leads to neurodegeneration through dysregulation of generic proteostatic mechanisms, specifically, the unfolded protein response. Genetic and pharmacological manipulation of the unfolded protein response was neuroprotective despite continuing prion replication, hence dissociating this from neurotoxicity. The data have clear implications for treatment across the spectrum of these disorders, targeting pathogenic processes downstream of protein misfolding.
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spelling pubmed-41063072014-07-23 Prions: Generation and Spread Versus Neurotoxicity Halliday, Mark Radford, Helois Mallucci, Giovanna R. J Biol Chem Minireviews Neurodegenerative diseases are characterized by the aggregation of misfolded proteins in the brain. Among these disorders are the prion diseases, which are transmissible, and in which the misfolded proteins (“prions”) are also the infectious agent. Increasingly, it appears that misfolded proteins in Alzheimer and Parkinson diseases and the tauopathies also propagate in a “prion-like” manner. However, the association between prion formation, spread, and neurotoxicity is not clear. Recently, we showed that in prion disease, protein misfolding leads to neurodegeneration through dysregulation of generic proteostatic mechanisms, specifically, the unfolded protein response. Genetic and pharmacological manipulation of the unfolded protein response was neuroprotective despite continuing prion replication, hence dissociating this from neurotoxicity. The data have clear implications for treatment across the spectrum of these disorders, targeting pathogenic processes downstream of protein misfolding. American Society for Biochemistry and Molecular Biology 2014-07-18 2014-05-23 /pmc/articles/PMC4106307/ /pubmed/24860100 http://dx.doi.org/10.1074/jbc.R114.568477 Text en © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles
spellingShingle Minireviews
Halliday, Mark
Radford, Helois
Mallucci, Giovanna R.
Prions: Generation and Spread Versus Neurotoxicity
title Prions: Generation and Spread Versus Neurotoxicity
title_full Prions: Generation and Spread Versus Neurotoxicity
title_fullStr Prions: Generation and Spread Versus Neurotoxicity
title_full_unstemmed Prions: Generation and Spread Versus Neurotoxicity
title_short Prions: Generation and Spread Versus Neurotoxicity
title_sort prions: generation and spread versus neurotoxicity
topic Minireviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106307/
https://www.ncbi.nlm.nih.gov/pubmed/24860100
http://dx.doi.org/10.1074/jbc.R114.568477
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