PLoS Pathog. 2010 Oct; 6(10): e1001138.

Published online 2010 Oct 7. doi: 10.1371/journal.ppat.1001138

PMCID: PMC2951383

Calcineurin Inhibition at the Clinical Phase of Prion Disease Reduces Neurodegeneration, Improves Behavioral Alterations and Increases Animal Survival

Abhisek Mukherjee et al

Prion diseases are a group of infectious neurodegenerative disorders producing a rapid and devastating clinical deterioration. The disease is 100% fatal and affected patients usually die within one year from the appearance of the first clinical alterations. Currently there is no treatment available for these diseases. The main goal of this study was to show that inhibition of the brain phophatase calcineurin is a therapeutic target for prion diseases. We show that calcineurin is hyperactivated as a consequence of endoplasmic reticulum stress produced by accumulation of misfolded prion protein. Treatment of animals showing the symptoms of prion disease with the calcineurin inhibitor FK506 resulted in a substantial decrease in the severity of clinical signs, an increase in animal survival and a reduction in brain degeneration. These findings indicate that calcineurin might play an important role in prion-induced neurodegeneration and inhibition of this phosphatase might represent a promising novel approach for prion disease therapy.

thanks but i have this paper already