Neurotoxicity of prion peptide 106‐126 not confirmed

Prion-related diseases are accompanied by neurodegeneration, astroglial proliferation and formation of proteinase K-resistant aggregates of the scrapie isoform of the prion protein (PrPSc). The synthetic PrP fragment 106-126 was reported to be neurotoxic towards cultured rat hippocampal neurons (Forloni, G., Angeretti, N., Chiesa, R., Monzani, E., Salmona, M., Bugiani, O. and Tagliavini, F. (1993) Nature 362, 543-546) and mouse cortical cells (Brown, D.R., Herms, J. and Kretzschmar, H.A. (1994) Neuroreport 5, 2057-2060). However, we found the viability of these and other neuronal cell types not to be impaired in the presence of PrP106-126 under widely varied sets of conditions. Aged preparations of the peptide as well as synthetic deamidated and isomerized derivatives that correspond to the aging products of the peptide proved also to lack neurotoxicity. Apparently, PrP106-126 cannot serve as a model for the interaction of PrP with neuronal cells.