The cellular
prion protein (PrP(C)), a
copper binding protein has a primary role in the pathogenesis of in
prion diseases. In these diseases alterations in the levels of
copper and
manganese have been described but how these alterations are involved in the pathogenesis is still unknown. Here we analysed synaptosomes of
scrapie infected mice and observed a significant reduction in the amount of
copper and an increase of the
manganese content at day 100 after
infection. Moreover a reduction of the
copper content in mouse brains induced by application of
copper poor diets was found to reduce the survival time of
scrapie infected mice significantly, whereas enhanced administration of
copper induced a significant delay in
prion disease onset. Interestingly a significant higher amount of PrP(C) full length and misfolded PK-resistant PrP was observed in mice that were treated with an enhanced
copper diet compared to controls. Moreover we could demonstrate that in healthy mock infected mice, a Cu(2+) rich/Mn(2+) poor diet induced a significantly decreased cleavage capability of PrP(C) compared to control mice. These new findings suggest that the
copper content in mouse brains exerts an influence on the amount of PrP(C) and its cleavage properties and may affect the PrP conversion by depleted availability of functional PrP full length.