Prion
Prion
Similar to Viruses Atypical Agents Small a Filterable Need host cells No machinery for energy generation of protein synthesis
Similar to Viruses Atypical Agents ▪ Small ▪ Filterable ▪ Need host cells ▪ No machinery for energy generation of protein synthesis
Different from viruses No detectable virions in infected tissues a No detectable virions in purified infectious material If nucleic acid is present, very small Very resistant
Different from viruses ▪ No dectectable virions in infected tissues ▪ No detectable virions in purified infectious material ▪ If nucleic acid is present, very small ▪ Very resistant
Resistant to or only Inactivated by partially inactivated 1 Autoclaving by 2. 5%sodium 1. Formaldehyde hypochlorite 2 Ethanol 3. Sodium hydroxide 3. Glutaraldehyde 4. Proteases, urea 4 Ultraviolet and other protein ionizing irradiation denaturants 5. Non-ionic detergents
▪ Resistant to or only partially inactivated by 1. Formaldehyde 2. Ethanol 3. Glutaraldehyde 4. Ultraviolet and ionizing irradiation 5. Non-ionic detergents ▪ Inactivated by 1. Autoclaving 2. 5%sodium hypochlorite 3. Sodium hydroxide 4. Proteases, urea, other protein denaturants
Pathogensis Kuru CUD(Creutzfeldt Jakob disease) GSS(Gerstmann Straussler-Scheinker syndrome) FFI(Fetal familial insomnia) Scrapie(sheep and goats) Bovine spongiform encephalopathy Transmissible mink encephalopathy Chronic wasting disease of mule deer
Pathogensis ▪ Kuru ▪ CJD(Creutzfeldt Jakob disease) ▪ GSS(Gerstmann Straussler-Scheinker syndrome) ▪ FFI(Fetal familial insomnia) ▪ Scrapie(sheep and goats) ▪ Bovine spongiform encephalopathy ▪ Transmissible mink encephalopathy ▪ Chronic wasting disease of mule deer
PRION PROTEIN(PrP) PrP PrPRES or PrPSc alpha- helical beta-pleated sheet protease sensitive protease resistant Helical- Happy Beta-pleated sheet-Bad
Simplified model for prion disease PrP PrPSC
Simplified model for prion disease
How can this model explain the sporadic, acquired or inherited form of the disease spontaneous conversion SPORADIC acquired conversion ACQUIRED acquired PrP germline mutation, spontaneous conversion more likely < INHERITED matic mutation, spontaneous conversion more likely SPORADIC
How can this model explain the sporadic, acquired or inherited form of the disease?
hy are there differences in prion diseases? PrP PrPSC PrP PrPs
Why are there differences in prion diseases?
germline mutation 1 INHERITED germline mutation 2 INHERITED disease caused by germline mutation 1 may differ from that caused by germline mutation 2