A synthetic peptide initiates Gerstmann-Straussler-Scheinker (GSS) disease in transgenic mice

Kiyotoshi Kaneko, Haydn L. Ball, Holger Wille, Hong Zhang, Darlene Groth, Marilyn Torchia, Patrick Tremblay, Jiri Safar, Stanley B. Prusiner, Stephen J. DeArmond, Michael A. Baldwin, Fred E. Cohen

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

The molecular basis of the infectious, inherited and sporadic forms of prion diseases is best explained by a conformationally dimorphic protein that can exist in distinct normal and disease-causing isoforms. We identified a 55-residue peptide of a mutant prion protein that can be refolded into at least two distinct conformations. When inoculated intracerebrally into the appropriate transgenic mouse host, 20 of 20 mice receiving the β-form of this peptide developed signs of central nervous system dysfunction at ~360 days, with neurohistologic changes that are pathognomonic of Gerstmann-Straussler-Scheinker disease. By contrast, eight of eight mice receiving a non-β-form of the peptide failed to develop any neuropathologic changes more than 600 days after the peptide injections. We conclude that a chemically synthesized peptide refolded into the appropriate conformation can accelerate or possibly initiate prion disease. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)997-1007
Number of pages11
JournalJournal of Molecular Biology
Volume295
Issue number4
DOIs
StatePublished - Jan 28 2000

Keywords

  • Gerstmann-Straussler-Scheinker (GSS) disease
  • PrP amyloid plaques
  • PrP mutation (P102L)
  • Prion protein synthetic peptide
  • β-pleated sheet

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Structural Biology

Fingerprint

Dive into the research topics of 'A synthetic peptide initiates Gerstmann-Straussler-Scheinker (GSS) disease in transgenic mice'. Together they form a unique fingerprint.

Cite this