Analysis of doppel protein toxicity

Taian Cui, Andrea Holme, Judyth Sassoon, David R. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The recently described doppel protein (Dpl) is a homologue of the prion protein (PrPc). This protein, expressed in the brains of mice that lack the expression of PrPc, causes neuronal death as the mice age. Previous studies have suggested this neuronal damage is caused by oxidative assault and changes in the activity of NOS proteins. We investigated the toxicity of Dpl in cell culture models and showed that Dpl was toxic to neurons. This toxicity was inhibited by the expression of PrPc and possibly involved direct interaction between the two proteins. The mechanism of toxicity involved stimulation of nitric oxide production via activation of the nitric oxide synthases, nNOS and iNOS. This mechanism of toxicity is quite different from that of PrPSc and does not require the protein to change conformation. These results provide the first evidence for the mechanism of Dpl toxicity.

Original languageEnglish
Pages (from-to)144-155
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume23
Issue number1
DOIs
Publication statusPublished - 1 May 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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