CYTOTOXICITY OF PRION PROTEIN PEPTIDE (PRP106-126) DIFFERS IN MECHANISM FROM THE CYTOTOXIC ACTIVITY OF THE ALZHEIMERS-DISEASE AMYLOID PEPTIDE, A-BETA-25-35

The abnormal form of the prion protein (PrPSc), a synthetic prion prot ein peptide fragment (PrP106-126) and fragments of the Alzheimer's pro tein precursor, APP, have been shown to be cytotoxic in vitro. We have used synchronous, clonal cell models originally developed to study th e toxicity of the Alzheimer's disease amyloid peptide, A beta 25-35, t o investigate the actions of PrP peptides. We found that the cytotoxic ity of the PrP106-126 depends on its state of aggregation and the cell ular expression of PrPC, and is independent of a loss of MTT reduction activity in the absence of cell death associated with the cellular ef fects of A beta 25-35. These factors may play a role in the lesion spe cificity of different pathological phenotypes of prion-protein related diseases. (C) 1996 Academic Press Limited.