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Title: Prions: Generation and Spread Versus Neurotoxicity
Authors: Halliday, Mark
Radford, Helois
Mallucci, Giovanna R.
First Published: 23-May-2014
Publisher: American Society for Biochemistry and Molecular Biology
Citation: The Journal of Biological Chemistry, 289, 19862-19868
Abstract: 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.
DOI Link: 10.1074/jbc.R114.568477
ISSN: 0021-9258
eISSN: 1083-351X
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Unported License applies to Author Choice Articles
Appears in Collections:Published Articles, MRC Toxicology Unit

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