NR ASJO
AU Fioriti,L.; Quaglio,E.; Massignan,T.; Colombo,L.; Stewart,R.S.; Salmona,M.; Harris,D.A.; Forloni,G.; Chiesa,R.
TI The neurotoxicity of prion protein (PrP) peptide 106-126 is independent of the expression level of PrP and is not mediated by abnormal PrP species
QU Molecular and Cellular Neurosciences 2005 Jan; 28(1): 165-76
PT journal article
AB A synthetic peptide homologous to region 106-126 of the prion protein (PrP) is toxic to cells expressing PrP, but not to PrP knockout neurons, arguing for a specific role of PrP in mediating the peptide's activity. Whether this is related to a gain of toxicity or a loss of function of PrP is not clear. We explored the possibility that PrP106-126 triggered formation of PrPsc or other neurotoxic PrP species. We found that PrP106-126 did not induce detergent-insoluble and protease-resistant PrP, nor did it alter its membrane topology or cellular distribution. We also found that neurons expressing endogenous or higher level of either wild-type PrP or a nine-octapeptide insertional mutant were equally susceptible to PrP106-126, and that sub-physiological PrP expression was sufficient to restore vulnerability to the peptide. These results indicate that PrP106-126 interferes with a PrP function that requires only low protein levels, and is not impaired by a pathogenic insertion in the octapeptide region.
MH Animals; Animals, Newborn; Cell Compartmentation/genetics; Cell Membrane/drug effects/metabolism; Cells, Cultured; Cytosol/metabolism; Down-Regulation/genetics; Hamsters; Mice; Mice, Transgenic; Mutation/genetics; Nerve Degeneration/*chemically induced/metabolism/physiopathology; Nerve Growth Factor/pharmacology; Neurons/drug effects/metabolism; Neurotoxins/genetics/metabolism/*toxicity; Peptide Fragments/genetics/metabolism/*toxicity; Prion Diseases/*genetics/*metabolism/physiopathology; Prions/*biosynthesis/genetics/metabolism/*toxicity; Rats; Research Support, Non-U.S. Gov't
AD Dulbecco Telethon Institute, Istituto di Ricerche Farmacologiche Mario Negri, Milan 20157, Italy.
SP englisch
PO USA