Theoretical analysis of the implication of PrP in neuronal death during transmissible subacute spongiform encephalopathies: Hypothesis of a PrP oligomeric channel

Transmissible subacute spongiform encephalopathies (TSE) are animal and hum an neurodegenerative diseases. The nature of the transmissible agent remain s unknown. The specific molecular marker of these diseases is the abnormal isoform of the prion protein (PrP). This protein is encoded by a cellular g ene and accumulates in a pathological isoform (PrPres) which is partially r esistant to proteolysis. The tridimensional structure of this protein remai ns theoretical. F. Cohen proposed one of the most realistic models. Accordi ng to this model and from molecular mechanics calculation, we suggest a PrP oligomeric ionic channel model that may be involved in TSE-induced neurona l apoptosis. (C) 2000 Academic Press.