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Recombinant prion protein does not possess SOD-1 activity
Samantha Jones1, Mark Batchelor, Daljit Bhelt
1MRC Prion Unit, Department of Neurodegenerative Diseases, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
The Biochemical Journal
|September 15, 2005
Summary
Prion protein (PrP) does not exhibit superoxide dismutase activity, contrary to previous claims. This finding suggests PrP’s role in oxidative stress is indirect, potentially regulating cellular responses rather than directly detoxifying free radicals.
Area of Science:
- Biochemistry
- Neuroscience
- Prion Biology
Background:
- Prion protein (PrP) is known to bind metal ions, particularly copper (II).
- Previous studies suggested that copper-bound PrP possesses superoxide dismutase (SOD) activity, implicating it in synaptic function and prion disease pathogenesis.
- The proposed loss of this SOD function during PrP(C) to PrP(Sc) conversion is linked to prion disease morbidity.
Purpose of the Study:
- To rigorously re-evaluate the claimed superoxide dismutase (SOD) activity of prion protein (PrP).
- To investigate whether copper (II) binding to PrP confers detectable SOD activity under various conditions.
Main Methods:
- Utilized a reliable assay procedure with a low detection limit (≥2 units of activity/mg of protein).
- Assayed both refolded PrP (in the presence of copper) and native PrP loaded with copper (II) ions.
- Compared PrP activity against baseline levels of copper (II) ions in water.
Main Results:
- Prion protein (PrP) exhibited no detectable superoxide dismutase (SOD) activity above the baseline levels of copper (II) ions in water.
- This lack of activity was consistent across assays performed on refolded and native PrP loaded with copper.
- The findings contradict previous reports suggesting PrP possesses SOD activity.
Conclusions:
- The prion protein (PrP) does not possess intrinsic superoxide dismutase (SOD) activity.
- If PrP influences oxidative stress, its role is likely indirect, possibly through the regulation of cellular protective responses.
- This challenges the hypothesis that loss of PrP's SOD function contributes to prion disease pathology.