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
Polythiophenes Inhibit Prion Propagation by Stabilizing Prion Protein (PrP) Aggregates
University of Zurich Hospital, Switzerland .
University of Zurich Hospital, Switzerland .
University of Zurich Hospital, Switzerland .
University of Zurich Hospital, Switzerland .
Show others and affiliations
2012 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, no 23, 18872-18887 p.Article in journal (Refereed) Published
Abstract [en]

Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here, we show that a variety of anionic, cationic, and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices and decreased the amount of scrapie isoform of PrPC (PrPSc) oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrPSc to proteolysis, triggered the compaction, and enhanced the resistance to proteolysis of recombinant mouse PrP(23-231) fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on cerebellar organotypic cultured slices and in vitro conversion assays with mouse PrP(23-231) indicated that poly(thiophene-3-acetic acid) may additionally interfere with the generation of PrPSc by stabilizing the conformation of PrPC or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrPSc deposits.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology , 2012. Vol. 287, no 23, 18872-18887 p.
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:liu:diva-79639DOI: 10.1074/jbc.M112.355958ISI: 000306411900001OAI: oai:DiVA.org:liu-79639DiVA: diva2:543971
Note

Funding Agencies|European Union P-7 Health||Swiss National Foundation||Novartis Research Foundation||European Research Council||Swedish Foundation for Strategic Research|FFL-4|

Available from: 2012-08-13 Created: 2012-08-13 Last updated: 2017-12-07

Open Access in DiVA

fulltext(898 kB)452 downloads
File information
File name FULLTEXT01.pdfFile size 898 kBChecksum SHA-512
358464b98c22a4ae63162cfe6a31aa6a414176df2d92b9c85db82b524436f5c151d67b12b8090d14d9191a07937040acc8d92f2091e978b5607ba1bfca359466
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Authority records BETA

Nyström, SofieHammarström, PerÅslund, AndreasNilsson, Peter

Search in DiVA

By author/editor
Nyström, SofieHammarström, PerÅslund, AndreasNilsson, Peter
By organisation
BiochemistryThe Institute of TechnologyOrganic ChemistryChemistryFaculty of Science & Engineering
In the same journal
Journal of Biological Chemistry
Engineering and Technology

Search outside of DiVA

GoogleGoogle Scholar
Total: 452 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: 164 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