Transmissible Spongiform Encephalopathies (TSEs) are a group of neurological disorders whose aetiological agent is believed to be PrPsc, an aberrant variant of the normal cellular prion protein PrPc, a GPI- anchored protein highly expressed in neuronal cells. Unlike PrPc, PrPsc is characterized by a higher β-sheet content (Pan et al., Proc. Natl. Acad. Sci. 90:10962-10966, 1993). Regarding the mechanisms of conversion of the cellular isoform in the aberrant one, a number of studies have been performed about a short peptide based on the sequence 106-126 of PrPc. It exhibits a prevalent β-sheet structure and forms amyloid fibrillar aggregates; since it has been shown to induce apoptosis in cultured cells, it might constitute the toxic core of PrPsc. In parallel, other peptides reproducing different portions of PrPc have been analysed, but their toxicity was found to be much less than with PrP[106-126] (Brown et al., J. of Inorg. Biochem., 98: 133-143, 2004). In the present work, we evaluated by MTT test the effect of several synthetic prion protein fragments on B104 neuroblastoma cells. These peptides (PrP[173-195], PrP[180-195] and several analogues) reproduce a region of PrPc corresponding to helic-2, that could be implicated in PrPc-PrPsc conversion because of its structural instability and its tendency to assume beta structure (Tizzano et al., Proteins 59(1): 72-9, 2005). We found a remarkable reduction of cell viability after 48 h of incubation of cells with PrP[173-195], so we suggest a reasonable role for this region in the anomalous misfolding of the scrapie isoform.
EFFECTS OF PRION PROTEIN FRAGMENTS ON THEPROLIFERATION OF B104 NEUROBLASTOMA CELLS
URSO, EMANUELA;MAFFIA, Michele
2006-01-01
Abstract
Transmissible Spongiform Encephalopathies (TSEs) are a group of neurological disorders whose aetiological agent is believed to be PrPsc, an aberrant variant of the normal cellular prion protein PrPc, a GPI- anchored protein highly expressed in neuronal cells. Unlike PrPc, PrPsc is characterized by a higher β-sheet content (Pan et al., Proc. Natl. Acad. Sci. 90:10962-10966, 1993). Regarding the mechanisms of conversion of the cellular isoform in the aberrant one, a number of studies have been performed about a short peptide based on the sequence 106-126 of PrPc. It exhibits a prevalent β-sheet structure and forms amyloid fibrillar aggregates; since it has been shown to induce apoptosis in cultured cells, it might constitute the toxic core of PrPsc. In parallel, other peptides reproducing different portions of PrPc have been analysed, but their toxicity was found to be much less than with PrP[106-126] (Brown et al., J. of Inorg. Biochem., 98: 133-143, 2004). In the present work, we evaluated by MTT test the effect of several synthetic prion protein fragments on B104 neuroblastoma cells. These peptides (PrP[173-195], PrP[180-195] and several analogues) reproduce a region of PrPc corresponding to helic-2, that could be implicated in PrPc-PrPsc conversion because of its structural instability and its tendency to assume beta structure (Tizzano et al., Proteins 59(1): 72-9, 2005). We found a remarkable reduction of cell viability after 48 h of incubation of cells with PrP[173-195], so we suggest a reasonable role for this region in the anomalous misfolding of the scrapie isoform.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
