Abnormal Brain Iron Homeostasis in Human and Animal Prion Disorders

Neurotoxicity in all prion disorders is believed to result from the accumulation of PrP-scrapie (PrPSc), a β-sheet rich isoform of a normal cell-surface glycoprotein, the prion protein (PrPC). Limited reports suggest imbalance of brain iron homeostasis as a significant associated cause of neurotoxicity in prion-infected cell and mouse models. However, systematic studies on the generality of this phenomenon and the underlying mechanism(s) leading to iron dyshomeostasis in diseased brains are lacking. In this report, we demonstrate that prion disease–affected human, hamster, and mouse brains show increased total and redox-active Fe (II) iron, and a paradoxical increase in major iron uptake proteins transferrin (Tf) and transferrin receptor (TfR) at the end stage of disease. Furthermore, examination of scrapie-inoculated hamster brains at different timepoints following infection shows increased levels of Tf with time, suggesting increasing iron deficiency with disease progression. Sporadic Creutzfeldt-Jakob disease (sCJD)–affected human brains show a similar increase in total iron and a direct correlation between PrP and Tf levels, implicating PrPSc as the underlying cause of iron deficiency. Increased binding of Tf to the cerebellar Purkinje cell neurons of sCJD brains further indicates upregulation of TfR and a phenotype of neuronal iron deficiency in diseased brains despite increased iron levels. The likely cause of this phenotype is sequestration of iron in brain ferritin that becomes detergent-insoluble in PrPSc-infected cell lines and sCJD brain homogenates. These results suggest that sequestration of iron in PrPSc–ferritin complexes induces a state of iron bio-insufficiency in prion disease–affected brains, resulting in increased uptake and a state of iron dyshomeostasis. An additional unexpected observation is the resistance of Tf to digestion by proteinase-K, providing a reliable marker for iron levels in postmortem human brains. These data implicate redox-iron in prion disease–associated neurotoxicity, a novel observation with significant implications for prion disease pathogenesis

OPTICAL AND OTHER PHYSICAL PROPERTIES OF Al (PO3)3 - CONTAINING FLUOROPHOSPHATE GLASSES

Dans cet article, on étudie les propriétés optiques et d'autres propriétés physiques de verre fluorophosphate comprenant le système à deux composantes de Al(PO3)3 et l'influence de divers fluorures sur ces propriétés dans le verre de basse teneur de Al(PO3)3. On donne le site de verre de basse teneur de Al(PO3)3 à la figure de nd∼ν, et une partie des propriétés de divers fluorures dans le verre est calculée.In this paper, the optical and some other physical properties of fluorophosphate glasses in binary systems containing Al(PO3)3 and the influence of various fluorides on the properties of glass with low Al(PO3)3 content have been studied. The positions of low Al(PO3)3 content glasses in nd∼ν diagram have been plotted and the partial properties of fluorides in glass have been calculated