The present invention relates to methods for the inhibition of disease-associated prion formation and propagation. Such methods are based on inhibition of PrP.sup.Sc cleavage, which prevents PrP.sup.Sc accumulation and results in reduced prion titers. More particularly, the present invention relates to endoproteolytic cleavage of PrP.sup.Sc by calpain, a calcium (Ca.sup.2+)-activated cysteine protease, and its inhibition.

 
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