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Prions: Generation and Spread Versus Neurotoxicity

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journal contribution
posted on 23.02.2016, 09:23 by Mark Halliday, Helois Radford, Giovanna R. Mallucci
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.

History

Citation

The Journal of Biological Chemistry, 289, 19862-19868

Version

VoR (Version of Record)

Published in

The Journal of Biological Chemistry

Publisher

American Society for Biochemistry and Molecular Biology

issn

0021-9258

eissn

1083-351X

Copyright date

2014

Available date

23/02/2016

Publisher version

http://www.jbc.org/content/289/29/19862

Language

en