Analysis of doppel protein toxicity

Taian Cui; Andrea Holme; Judyth Sassoon; David R. Brown

doi:10.1016/S1044-7431(03)00017-4

Analysis of doppel protein toxicity

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

^*Corresponding author for this work

University of Bath

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

Abstract

The recently described doppel protein (Dpl) is a homologue of the prion protein (PrP^c). This protein, expressed in the brains of mice that lack the expression of PrP^c, 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 PrP^c 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 PrP^Sc and does not require the protein to change conformation. These results provide the first evidence for the mechanism of Dpl toxicity.

Original language	English
Pages (from-to)	144-155
Number of pages	12
Journal	Molecular and Cellular Neuroscience
Volume	23
Issue number	1
DOIs	https://doi.org/10.1016/S1044-7431(03)00017-4
Publication status	Published - 1 May 2003
Externally published	Yes

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AU - Brown, David R.

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AB - 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.

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Analysis of doppel protein toxicity

Abstract

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