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Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
12:57

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans

Published on: January 8, 2015

Cellular prion protein expression is not regulated by the Alzheimer's amyloid precursor protein intracellular domain

Victoria Lewis1, Isobel J Whitehouse, Herbert Baybutt

  • 1Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.

Plos One
|February 25, 2012
PubMed

Insights

This study investigated the link between Alzheimer's disease (AD) and prion diseases, finding that the APP intracellular domain (AICD) does not significantly alter cellular prion protein (PrP(C)) levels in cell or animal models.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Growing evidence links Alzheimer's disease (AD) and prion diseases at molecular and cellular levels.
  • Cellular prion protein (PrP(C)) influences amyloid precursor protein (APP) processing, and APP intracellular domain (AICD) may regulate PrP(C) expression.

Purpose of the Study:

  • To clarify the role of AICD in regulating PrP(C) expression.
  • To investigate the molecular links between AD and prion diseases.

Main Methods:

  • Utilized transgenic mice and cell culture models.
  • Manipulated APP expression and processing, including over-expression of APP isoforms and knockdown of endogenous APP.
  • Inhibited γ-secretase activity.

Main Results:

  • Over-expression of human APP isoforms in cells did not affect endogenous PrP(C) levels.
  • Transgenic mice over-expressing wild-type or mutant human APP showed unaltered PrP(C) levels in brain tissue.
  • APP knockdown or γ-secretase inhibition did not alter PrP(C) levels.

Conclusions:

  • The study found no significant difference in PrP(C) expression across various experimental paradigms.
  • The previously suggested straightforward control of cellular PrP(C) levels by AICD was not supported by these findings.

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