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 (PrP(c)) into abnormal protease resistant PrP(Sc) 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 Abeta 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 PrP(Sc) aggregates and modify their subcellular localization. Despite the fact that trehalose does not modify the protease resistance properties of PrP(Sc) molecules, it significantly protects prion-infected cells from induced oxidative damage, suggesting that this compound is of therapeutic interest.
Béranger
Florence
F
Institut de Génétique Humaine, UPR CNRS1142, 141 Rue de Cardonille, 34396 Montpellier Cedex 5, France. inserm-usa@ambafrance-us.org
Crozet
Carole
C
Goldsborough
Andrew
A
Lehmann
Sylvain
S
D000818:Animals; D002460:Cell Line; D019610:Cytoprotection; D003902:Detergents / Q000737:chemistry; D019286:Endopeptidase K / Q000737:chemistry; D051379:Mice; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D018620:PrPSc Proteins / Q000737:chemistry / Q000378:metabolism*; D014199:Trehalose / Q000494:pharmacology*
D003902:Detergents; D018620:PrPSc Proteins; D014199:Trehalose; D019286:Endopeptidase K