Overexpressed protein disulfide isornerase in brains of patients with sporadic Creutzfeldt-Jakob disease

Earlier studies have failed to detect covalent modifications in P-sheet-rich scrapie isoform prion protein (PrPSc) and have concluded that the conversion of a-helix-rich cellular form prion protein (PrPC) to PrPSc represents purely conformational transition not involving chemical reactions. However, recent studies have shown that the intradisulfide bond of PrPC can play an important role for instability and conformational change to PrPSc. Interestingly, we found overexpressed protein disufide isomerase (PDI) in brains of sporadic Creutzfeldt-Jakob disease (sCJD, human prion disease) patients using two dimensional electrophoresis and Western blot analysis but not in other neurodegenerative disorders as Down Syndrome and Alzheimer's disease. However, proteinase K digestion and plasminogen binding assay of brain homogenates incubated with PDI suggest that PDI has no effect on either proteinase resistance or conformational change of PrP. Overexpression of PDI protein in sCJD brain may simply reflect a cellular defense response against the altered prion protein. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.