TransmissibleSpongiformEncephalopathyPrionProtein.pptVIP

Transmissible Spongiform Encephalopathy Prion Protein Diseases Lisa Kennedy, Dylan Bradford, Madi Hoagland Henefield, Anders Ohman Advisor: Dr. Todd Livdahl Background Types of TSE Molecular Biology of the Pathogenesis of TSE Prion disease are unique in that they are transmissible particles that lack any form of nucleic acid, and yet are still infectious Prusiner, 1998 . While prion diseases are not completely understood, it is clear the disease is caused by an accumulation in the brain of a misfolded cellular protein known as the prion protein PrPc Campana et al., 2008 . The normally occurring prion protein is converted into the modified infectious protein PrPSc posttranslationally. During this process PrPc misfolds into PrPSc which contains a high number of β-sheets. The process during which the normal protein changes to the abnormal takes place when some of the α-helices and coils of its structure refold into β-sheets. This structural alteration causes less understood but still profound changes in the chemical properties of the PrP. The changes that result in the PrPSc have been shown to act as a template upon which PrPc is refolded into PrPSc Prusiner, 1998 . This is how the misfolded protein is able to become infectious to other prion proteins around it. Furthermore, PrPSc has shown the ability to resist degradation even after the death of its host for up to months or even years at a time, and still be infectious to a new host if picked up. Modeling the System 1921: Creutzfeldt-Jakob disease CJD Kuru: 1959 1732*: Scrapie 1936: Gerstmann Straussler-Scheinker Syndrome GSSS 1947: Transmissible mink encephalopathy 2003: Feline spongiform encephalopathy 1967: Chronic Wasting Disease CWD: captivity 1974: Fatal Familial Insomnia 1981: CWD wild populations 1986: BSE 1996: Variant Creutzfeldt-Jakob Disease *Timeline not to scale **The dates indicate descriptions and identifications of the respective diseases. At the earlier dates, cause of di