Neurotoxicity but not infectivity of prion proteins can be induced reversibly in vitro

Prion diseases include Creutzfeldt-Jakob disease in humans, scrapie in shee p and bovine spongiform encephalopathy. The hallmark of prion diseases is t he accumulation of an abnormal isoform (PrPSc) of the cellular prion protei n accompanied by neuronal cell death and astroglial proliferation. To chara cterize the correlation between PrP secondary and quarternary structure and their biological effects we assayed soluble and aggregated forms of PrP 27 -30, the N-terminal truncated form of PrPSc, as well as the corresponding r ecombinant PrP(90-231) for their neurotoxicity and infectivity. PrP was kep t soluble in 0.2% SDS and subsequently reaggregated either by diluting the SDS or by adding acetonitril. The neurotoxicity of the re-aggregated states were comparable to that of prion rods (PrP 27-30) whereas the soluble form s had no neurotoxic effects. The solubilized PrP 27-30 showed no significan t infection upon re-aggregation as determined by bioassays in Syrian golden hamsters. The recombinant PrP did not exhibit infectivity in any state.