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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Biochemistry and Molecular Biology
2014
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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. |
format | Online Article Text |
id | pubmed-4106307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hallidaymark prionsgenerationandspreadversusneurotoxicity AT radfordhelois prionsgenerationandspreadversusneurotoxicity AT malluccigiovannar prionsgenerationandspreadversusneurotoxicity |