Recombinant prion protein does not possess SOD-1 activity.

A considerable body of evidence now shows that PrP (prion protein) binds metal ions with high affinity and it has been claimed that the binding of copper (II) ions to PrP confers SOD (superoxide dismutase) activity. In turn, it has been suggested that PrP is a synaptic dismutase and that loss of this function, as a result of the conversion of PrP(C) into PrP(Sc), results in pathology and hence morbidity associated with prion disease. However, contrary to previous reports, in the present study we have found that PrP exhibits no detectable dismutase activity above baseline levels measured for copper (II) ions in water when assayed using a reliable procedure with a detection limit of at least 2 units of activity/mg of protein. This was true when the assay was performed with either PrP refolded from a denatured state in the presence of copper, as in previous studies, or native PrP loaded with copper. Thus if PrP has any role in oxidative stress, it must be indirect as a regulator of protective cellular responses.