NEW! BSE Copper and Manganese hmmm... sounds familiar

[Kathy]

So the truth will be told:

Brain Res. 2009 Jul 24.
Role of copper and manganese in prion disease progression.

Mitteregger G, Korte S, Shakarami M, Herms J, Kretzschmar HA.
Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Feodor-Lynen-Str. 23, 81377 Munich, Germany.

The cellular prion protein (PrP(C)), a copper binding protein has 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.

PMID: 19635464

Back to the beginning, Mark Purdey's findings, and asking the important question, "why is manganese content in the brain upregulated in prion diseases?"

Med Microbiol Immunol. 2009 Jul 25.

Manganese-induced changes of the biochemical characteristics of the recombinant wild-type and mutant PrPs.

Li XL, Dong CF, Wang GR, Zhou RM, Shi Q, Tian C, Gao C, Mei GY, Chen C, Xu K, Han J, Dong XP.
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying-Xin Rd 100, Beijing, 100052, People's Republic of China.

Manganese may play some roles in the pathogenesis of prion diseases. In this study, recombinant human wild-type (WT) PrP and PrP mutants with deleted or inserted octarepeats were exposed to manganese, and their biochemical and biophysical characteristics were evaluated by proteinase K (PK) digestion, sedimentation experiments, transmission electron microscopy and circular dichroism. It demonstrated that incubation of manganese remarkably increased PK-resistances, protein aggregations and beta-sheet contents of the PrPs. Moreover, the PrP mutants of inserted or deleted octarepeats were much vulnerable to the influence of manganese, which showed obviously more aggregation and higher beta-sheet content than that of WT-PrP. It highlights that the effect of manganese on the PrP seems to lie on the incorrectness of the octarepeats numbers. The association of the octarepeats number of PrP with manganese may further provide insight into the unresolved biological function of PrP in the neurons.

PMID: 19633867