liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Defining the Conformational Features of Anchorless, Poorly Neuroinvasive Prions
Department of Pathology, University of California, San Diego, La Jolla, California, United States of America.
Department of Pathology, University of California, San Diego, La Jolla, California, United States of America.
Department of Pathology, University of California, San Diego, La Jolla, California, United States of America.
Department of Neuroscience, University of California, San Diego, La Jolla, California, United States of America.
Show others and affiliations
2013 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 9, no 4Article in journal (Refereed) Published
Abstract [en]

Infectious prions cause diverse clinical signs and form an extraordinary range of structures, from amorphous aggregates to fibrils. How the conformation of a prion dictates the disease phenotype remains unclear. Mice expressing GPI-anchorless or GPI-anchored prion protein exposed to the same infectious prion develop fibrillar or nonfibrillar aggregates, respectively, and show a striking divergence in the disease pathogenesis. To better understand how a prion's physical properties govern the pathogenesis, infectious anchorless prions were passaged in mice expressing anchorless prion protein and the resulting prions were biochemically characterized. Serial passage of anchorless prions led to a significant decrease in the incubation period to terminal disease and altered the biochemical properties, consistent with a transmission barrier effect. After an intraperitoneal exposure, anchorless prions were only weakly neuroinvasive, as prion plaques rarely occurred in the brain yet were abundant in extracerebral sites such as heart and adipose tissue. Anchorless prions consistently showed very high stability in chaotropes or when heated in SDS, and were highly resistant to enzyme digestion. Consistent with the results in mice, anchorless prions from a human patient were also highly stable in chaotropes. These findings reveal that anchorless prions consist of fibrillar and highly stable conformers. The additional finding from our group and others that both anchorless and anchored prion fibrils are poorly neuroinvasive strengthens the hypothesis that a fibrillar prion structure impedes efficient CNS invasion.

Place, publisher, year, edition, pages
Public Library of Science , 2013. Vol. 9, no 4
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:liu:diva-96155DOI: 10.1371/journal.ppat.1003280ISI: 000318072700023OAI: oai:DiVA.org:liu-96155DiVA: diva2:640715
Available from: 2013-08-14 Created: 2013-08-14 Last updated: 2017-12-06

Open Access in DiVA

fulltext(12786 kB)307 downloads
File information
File name FULLTEXT01.pdfFile size 12786 kBChecksum SHA-512
6fdc7261f4a5855232983a3c142bd02eab31a3423f95711470d70905829bd22b0c3c04587355ed9d5676104fdad35b04ee37cf902943efecc1453a348f1b5c07
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Authority records BETA

Nilsson, Peter

Search in DiVA

By author/editor
Nilsson, Peter
By organisation
ChemistryThe Institute of Technology
In the same journal
PLoS Pathogens
Engineering and Technology

Search outside of DiVA

GoogleGoogle Scholar
Total: 307 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 126 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf