Test 3 - Prions Flashcards
Human genetical prion disease includes… (3)
- Fatal Familiar Insomnia
- Gerstmann-Straussler Syndrome
- Creutzelds-Jakob Disease
Human non-genetic prion disease includes…
Kuru
Prion is unique as an pathogen because it..
can cross species easily.
Prion Discovery: First Step? Basis of the step? What is classified as originally?
Viral v Bacterial: Filter. Size. If bacterial, in retentate. If viral, in flow-through. Prion was in FT.
Prion Discovery: Second Step? Basis of the step? What was it classified as?
DNA or RNA: Treating with DNA or RNA. Basis that treating with same nucleic acid will cause loss of infectivity. (If DNA, treating with DNA –> Loss of infectivity. IF RNA, treating with RNA–> loss of infectivity. Classified as neither.
Prion Discovery: Third Step? Why did they chose to do this? Theoretical basis of the step? What was it classified as?
Radiation Bombardment, because 2nd step thought not to work because genetic material is too tightly bound. If DNA/RNA, radiation will cause loss of infectivity. Classified as NOT a nucleic acid!!!
Prion Discovery: The Last Step? Basis of the step? What was it classified as?
Protease Treatment. Hypothesis that if protein, prion will lose infectivity. Infectious agent is protein.
What causes scabies?
PrP^(sc)
What are the characteristics of PrPsc? What is it involved in?
PrPsc is very stable and binds to Ca2+. May be involved in stem cells, long term memory, or neuronal repair.
The similarities between PrPsc and PrPc is…
1’ Structure – Same AA sequence.
The difference between PrPsc and PrPc is…
2’ Structure – Different Folding. PrPsc is mostly ß sheets, while PrPc is mostly α helixes.
α helixes makes __1__ (soluble/insoluble) and (protease sensitive/resistant)
α helixes makes PrPc soluble and protease sensitive
ß sheets makes__1__ (soluble/insoluble) and (protease sensitive/resistant). Why is it resistant/sensitive?
ß sheets makes PrPsc insoluble and protease resistant. Resistant because ++stability. (Hence High ∆G++)
Prion Disease grows in a … pattern.
Exponential
Prion disease manifests itself in … in autopsied samples
long polymers of PrPsc
What is the Heterodimer Model of Prion Disease? What does it explain? What doesn’t it explain?
PrPc and PrPsc bind to create a Heterodimer. AND THEN, PrPsc acts as an enzyme to convert PrPc –> PrPsc. This explains exponential growth (due to + loop). This does not explain polymers or the fact that monomers of PrPsc are never seen in autopsy.
What is the Polymerization Model of Prion Disease? What does it explain? What doesn’t it explain?
PrPsc reacts with PrPc and makes PrPc–>PrPsc before they bind together to form polymers. It explains polymers but does not explain why the growth is exponential (this model predicts linear growth).
What is the ADDENDUM TO Polymerization Model of Prion Disease? What does it explain? What doesn’t it explain?
Polymers of PrPsc can break off to create another strand of polymer. It explains exponential growth, but cannot explain how the polymers break up in the first place.
Infection: Prion disease has a short incubation period (T/F)
F
Infection: What are the 3 forms of prion disease?
- Acquired Prion Disease.
- Sporadic PD
- Familiar PD
Infection: Acquired PD is from… (examples?)
coming into contact with infectious agent, like corneal transplant or tainted meat.
Infection: Sporadic PD is from…
Random conversion of PrPc to PrPsc, which is VERY rare due to ∆G++.
Infection: Familiar PD is from…
Mutation in PRNP Gene, which codes for PrPc. This mutation makes PrPc–>PrPsc more likely by lowering ∆G++. Families have a predisposition to acquiring prion disease because of this.
What was the difference of onset of Prion Disease in PrPc-Knockout Mice and mice with overexpressed PrPc?
Immunity v. rapid onset.
