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Prion diseases cause iron imbalance

March 17, 2009 at 10:14 AM   |   Comments

CLEVELAND, March 17 (UPI) -- A U.S. study suggests an imbalance of iron homeostasis is a common feature of prion disease-affected human, mouse and hamster brains.

Dr. Neena Singh and colleagues at Case Western Reserve University School of Medicine and Creighton University said their findings provide insight into the mechanism of neurotoxicity in prion disorders and might lead to the development of new therapeutic strategies.

Unlike other neurodegenerative conditions, prion disorders are sporadic, inherited and infectious, affecting both humans and animals, the scientists said, citing as examples mad cow disease in cattle, scrapie in sheep and Creutzfeldt-Jakob disease in humans. The causative agent of all the maladies is a misfolded protein referred to as PrP-scrapie that replicates itself by changing the conformation of neighboring copies of the same protein, namely the prion protein.

The new research suggests accumulations of PrP-scrapie alter the metabolism of iron in diseased brains. The imbalance of brain iron homeostasis worsens with disease progression and isn't an outcome of end-stage disease. And, the researchers added, since iron is highly toxic when mismanaged, the condition is likely to contribute significantly to prion-disease-associated neurotoxicity.

Singh and her team said they were surprised to find prion disease-affected brains are iron deficient despite a significant increase in their overall iron content.

The findings are reported in the journal PLoS Pathogens.

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