Highly infectious prions are not directly neurotoxic.
neurodegeneration
neurotoxicity
prions
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
22 09 2020
22 09 2020
Historique:
pubmed:
10
9
2020
medline:
18
11
2020
entrez:
9
9
2020
Statut:
ppublish
Résumé
Prions are infectious agents which cause rapidly lethal neurodegenerative diseases in humans and animals following long, clinically silent incubation periods. They are composed of multichain assemblies of misfolded cellular prion protein. While it has long been assumed that prions are themselves neurotoxic, recent development of methods to obtain exceptionally pure prions from mouse brain with maintained strain characteristics, and in which defined structures-paired rod-like double helical fibers-can be definitively correlated with infectivity, allowed a direct test of this assertion. Here we report that while brain homogenates from symptomatic prion-infected mice are highly toxic to cultured neurons, exceptionally pure intact high-titer infectious prions are not directly neurotoxic. We further show that treatment of brain homogenates from prion-infected mice with sodium lauroylsarcosine destroys toxicity without diminishing infectivity. This is consistent with models in which prion propagation and toxicity can be mechanistically uncoupled.
Identifiants
pubmed: 32900920
pii: 2007406117
doi: 10.1073/pnas.2007406117
pmc: PMC7525444
doi:
Substances chimiques
Neurotoxins
0
Prions
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23815-23822Subventions
Organisme : Medical Research Council
ID : MC_U123192748
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_1004/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/7
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U12266B
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M02492X/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: J.C. is a Director and J.C. and J.D.F.W. are shareholders of D-Gen Limited, which supplied one antibody used in the study.
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