Trehalose impairs aggregation of PrPSc molecules and protects prion-infected cells against oxidative damage

Neurodegenerative disorders such as Alzheimer's, Huntington's, and prion diseases are characterized by abnormal protein deposits in the brain of affected patients. in prion diseases, a key event in the pathogenesis is the conversion of the normal prion protein (PrPC) into abnormal protease resistant PrPSc deposits, a phenomenon associated with a higher sensitivity to oxidative stress in vitro. In cellular models of Alzheimer and Huntington diseases, the disaccharide trehalose has been shown to be effective in inhibiting huntingtin and A beta peptide aggregates and reducing their associated toxicity. We show in this study that trehalose treatment of prion-infected cells decreases the size of de novo produced PrPSc aggregates and modify their subcellular localization. Despite the fact that trehalose does not modify the protease resistance properties of PrPSc molecules, it significantly protects prion-infected cells from induced oxidative damage, suggesting that this compound is of therapeutic interest. (C) 2008 Elsevier Inc. All rights reserved.