Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion

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Updated: Jul 25, 2026

Protein Misfolding Cyclic Amplification of Prions
10:12

Protein Misfolding Cyclic Amplification of Prions

Published on: November 7, 2012

G C Telling1, P Parchi, S J DeArmond

  • 1Department of Neurology, University of California, San Francisco, CA 94143, USA.

Science (New York, N.Y.)
|December 20, 1996
PubMed

Insights

Fatal familial insomnia (FFI) involves a distinct prion protein (PrPSc) conformation, differing from other prion diseases. This conformational difference dictates prion strain diversity and disease transmission.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Protein Chemistry

Background:

  • Prion diseases involve the misfolding of cellular prion protein (PrPC) into a pathogenic form (PrPSc).
  • Fatal familial insomnia (FFI) is a distinct prionopathy characterized by a unique PrPSc fragment size (19 kDa) compared to other prion diseases (21 kDa).

Purpose of the Study:

  • To investigate the role of PrPSc conformation in prion disease pathogenesis and strain diversity.
  • To determine if FFI-associated PrPSc can induce disease with its characteristic conformation in a susceptible model.

Main Methods:

  • Transmission of brain extracts from FFI and Creutzfeldt-Jakob disease (CJD) patients to transgenic mice expressing human-mouse chimeric PrP.
  • Analysis of the protease-resistant PrPSc fragment size after deglycosylation in infected mice.

Main Results:

  • FFI brain extracts transmitted disease to transgenic mice, inducing the 19 kDa PrPSc fragment.
  • CJD brain extracts induced the 21 kDa PrPSc fragment in the same mouse model.
  • Demonstrated that PrPSc conformation dictates the formation of nascent PrPSc.

Conclusions:

  • The conformation of PrPSc acts as a template, guiding the conversion of normal PrPC.
  • Prion strain diversity is encoded within the distinct conformations of PrPSc.
  • This conformational templating mechanism explains the existence of different prion strains.

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