Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding

Gabriela P. Saborio (), Bruno Permanne and Claudio Soto ()
Additional contact information
Gabriela P. Saborio: Serono Pharmaceutical Research Institute
Bruno Permanne: Serono Pharmaceutical Research Institute
Claudio Soto: Serono Pharmaceutical Research Institute

Nature, 2001, vol. 411, issue 6839, 810-813

Abstract: Abstract Prions are the infectious agents responsible for transmissible spongiform encephalopathies. The principal component of prions is the glycoprotein PrPSc, which is a conformationally modified isoform of a normal cell-surface protein called PrPC (ref. 1). During the time between infection and the appearance of the clinical symptoms, minute amounts of PrPSc replicate by conversion of host PrPC, generating large amounts of PrPSc aggregates in the brains of diseased individuals. We aimed to reproduce this event in vitro. Here we report a procedure involving cyclic amplification of protein misfolding that allows a rapid conversion of large excess PrPC into a protease-resistant, PrPSc-like form in the presence of minute quantities of PrPSc template. In this procedure, conceptually analogous to polymerase chain reaction cycling, aggregates formed when PrPSc is incubated with PrPC are disrupted by sonication to generate multiple smaller units for the continued formation of new PrPSc. After cyclic amplification more than 97% of the protease-resistant PrP present in the sample corresponds to newly converted protein. The method could be applied to diagnose the presence of currently undetectable prion infectious agent in tissues and biological fluids, and may provide a unique opportunity to determine whether PrPSc replication results in the generation of infectivity in vitro.

Date: 2001
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/35081095 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:411:y:2001:i:6839:d:10.1038_35081095

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35081095

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().