A protease-resistant 61-residue prion peptide causes neurodegeneration in transgenic mice

S. Supattapone, E. Bouzamondo, H. L. Ball, H. Wille, H. O B Nguyen, F. E. Cohen, S. J. DeArmond, S. B. Prusiner, M. Scott

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Abstract

An abridged prion protein (PrP) molecule of 106 amino acids, designated PrP106, is capable of forming infectious miniprions in transgenic mice (S. Supattapone, P. Bosque, T. Muramoto, H. Wille, C. Aagaard, D. Peretz, H.-O. B. Nguyen, C. Heinrich, M. Torchia, J. Safar, F. E. Cohen, S. J. DeArmond, S. B. Prusiner, and M. Scott, Cell 96:869-878, 1999). We removed additional sequences from PrP106 and identified a 61-residue peptide, designated PrP61, that spontaneously adopted a protease-resistant conformation in neuroblastoma cells. Synthetic PrP61 bearing a carboxy-terminal lipid moiety polymerized into protease-resistant, β-sheet-enriched amyloid fibrils at a physiological salt concentration. Transgenic mice expressing low levels of PrP61 died spontaneously with ataxia. Neuropathological examination revealed accumulation of protease-resistant PrP61 within neuronal dendrites and cell bodies, apparently causing apoptosis. PrP61 may be a useful model for deciphering the mechanism by which PrP molecules acquire protease resistance and become neurotoxic.

Original languageEnglish (US)
Pages (from-to)2608-2616
Number of pages9
JournalMolecular and cellular biology
Volume21
Issue number7
DOIs
StatePublished - Mar 28 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Supattapone, S., Bouzamondo, E., Ball, H. L., Wille, H., Nguyen, H. O. B., Cohen, F. E., DeArmond, S. J., Prusiner, S. B., & Scott, M. (2001). A protease-resistant 61-residue prion peptide causes neurodegeneration in transgenic mice. Molecular and cellular biology, 21(7), 2608-2616. https://doi.org/10.1128/MCB.21.7.2608-2616.2001