Molecular pathogenesis of transmissible spongiform encephalopathy

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Molecular pathogenesis of prion disease was studied based on the analysis of prion protein (PrP) gene.Several new findings were also obtained from the studies on animal models.Involevement of polymorphisms of PrP gene in the onset of prion disease was indicated, especially in term of correlation of codon 219 with sporadic Creutzfeldt-Jakob disease as a unique feature of Japanese.Correlation of PrP gene mutation with transmission of the disease to mice was also demonstrated.Transgenic mice overexpressing human PrP gene was produced and found to be highly susceptible to CJD.Biochemical profiles of the brain of CJD patient was demonstrated in term of gangliosides.Resistance of PrPSc to proteinase K was shown to correlate with the incubation period of scrapie in mice, and passages in mice brain was suggested to cause increased aggregation of PrPSc.Studies of prion-less neural cells suggested an involvement of apoptosis in the cell death.In vitro model of the conformational change of protein showed temperature-dependent conversion from alpha-helix to beta-sheet.As an animal model of spongiform encephalopathy, zitter rats were studied in terms of zi gene and involvement of super-oxide in pathogenesis.Investigation on spontaneous spongiform encephalopathy in pets and birds could not find such cases.