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Updated: Aug 8, 2026

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain
11:29

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain

Published on: October 3, 2012

PrPSc-like prion protein peptide inhibits the function of cellular prion protein

D R Brown1

  • 1Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, U.K. drb33@cam.ac.uk

The Biochemical Journal
|November 22, 2000
PubMed

Insights

Mice without prion protein are protected from prion disease. The abnormal prion protein isoform (PrPSc) interacts with normal prion protein, potentially causing neurodegeneration by inhibiting its function and increasing copper toxicity.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Molecular Biology

Background:

  • Prion diseases are fatal neurodegenerative disorders.
  • The normal cellular prion protein (PrP) is essential for disease development.
  • The abnormal, disease-associated isoform is PrPSc.

Purpose of the Study:

  • To investigate the interaction between PrPSc and cellular PrP.
  • To determine the functional consequences of this interaction on PrP function and cellular susceptibility to toxicity.

Main Methods:

  • Binding assays to identify interaction sites between PrPSc/PrP106-126 and cellular PrP.
  • Cellular assays to assess copper toxicity, copper uptake, and superoxide dismutase-like activity.

Main Results:

  • PrPSc and the PrP106-126 peptide bind to cellular PrP at residues 112-119.
  • This interaction leads to the stripping of PrP from cells.
  • PrP106-126 binding increases cellular copper toxicity, inhibits copper uptake, and impairs PrP's superoxide dismutase-like activity.

Conclusions:

  • Direct interaction between PrPSc and cellular PrP is crucial for prion disease pathogenesis.
  • Inhibition of normal PrP function by PrPSc may be a key mechanism driving neurodegeneration.
  • Understanding these interactions could inform therapeutic strategies for prion diseases.

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