Prion disease - Basic science (Dr Wille) Flashcards

(37 cards)

1
Q

What is the first prion disease that was described?

A

Scrapie

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2
Q

Is scrapie transmissible to humans?

A

No. Only contagious to sheep and goats; forms holes in their brains

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3
Q

What are the 3 manifestations of human prion disease?

A
  • Sporaic: Creutzfeldt-Jakob disease (1920s)
  • Inherited: Germlines mutation in PRNP gene (usually dominant)
  • Infection: Transmitted via canibalism, medical procedures, consumption of infected fppd
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4
Q

What is most common of human prion disesae?

A

Sporadic (90%); familial (10%); infectious (1%)

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5
Q

What are the death chances w/ prion disease?

A

1:5000

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6
Q

What is kuru?

A

Prion disease trasmitted via ritualistic cannibalism in Fore tribe; discovered by Dr. Carleton Gajdusek;

Slow disease (5-50 years incubation); now extinct

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7
Q

What is bovine spongiform encephalopathy?

A
  • Caused by feeding meat and bone meal to cattle (industrial cannibalism) –> mad cow’s disease
  • No contamination to pastures like scrapie
  • Three strains: classical; atypical and genetic
  • Classical is transmitted to humans
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8
Q

What is the diff between sporadic CJD and variant CJD?

A

Sporadic affects elderly; variant affects younger

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9
Q

How many people showed signs of abnormal PrP deposits?

A

Apenndixes showed 1:2000 in Great Britain; high prevalence

Tonsils and appendix are where prions show up first

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10
Q

Where is chronic wasting disease found?

A

Deer, elk moos

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11
Q

Does CWD transmit via tissue, feces, saliva, urine?

A

YES. It is the most infectious prion disease we know

Slide 17

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12
Q

TRUE or false: are caribou threatened?

A

Yes, but it has not been trasnmitted yet

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13
Q

TRUE or False: Cooking reduces infectivity substantially

A

False, only marginally

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14
Q

Describe the overall human-human transmissions:

A
  • Kuru: very efficient, not a problem anymore
  • Iatrogenic CJD: very efficient, may be problem in UK
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15
Q

Describe the overall cattle-human transmissions:

A

BSE: Primary transmission relatively inefficient, incubation period uncertain; documented secondary transmirrion (eg blood transfusion)

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16
Q

Describe the overall sheep/goat-human transmissions:

A

Scrapie: no documented transmission, exposure suspected to be widespread.

17
Q

Describe the overall deer/elk/moose-human transmissions:

A

CWD: Well documented exposure in increasing numbers, but no transmission so far; transmisison to non-human primates have been recorded

18
Q

Is a prion a virus?

19
Q

Where do prions first show up?

A

Specialized population of immune cells in illeum; peyers patch; these cells sample content of gut and present antigens to immune cells on other side (trains antigens to not be allergic to food); however they are also** responsible to transport prions **

immune cells can get infected and spread prions

20
Q

How are prions taken up in the nervous sys?

A

Vagus nerve, mesenteric ganglion complex

21
Q

What is a prion?

A
  • Proteinacrous infectious particles
  • Pathogens
  • Composed of only protein
  • Devoid of nucleic acid
  • Coded by PRNP
  • Can be folded into an infectious form PrpSc
22
Q

Describe diff. between PrpC, PrpSc

A

PrpC: non infectious; cellular form of prion protein; PrpSc: infectious form, can be insoluble, resistant to proteolysis

23
Q

What is Prp 27-30?

A

N-terminal truncation of PrpSc, still infectious

24
Q

What is recPrp

A

recombinant, bacterially expressed prion protein, no post-translation moD.

not automatically infectious

25
What dogmas did the prion hypothesis break?
1. All infectious agents have DNA or RNA (virology dogma) 2. Info flows from DNA to rna to proteins only (mol. bio dogma) 3. Native structure of a protein only determiend by amino acid seq (Anfinsen's dogma)
26
What does GP1 do?
Anchors prion protein
27
What are ZIPs?
Prion protein ancestor; first exon went through retrotransposon event and became PrP gene; part of the **SLC39 family** - they have Irt-like proteins, Zn2+ transporters
28
Is Prnp found in lower vertebrates?
No
29
TRUE or FALSE: prion disease occurs in non mammals
False
30
Why is it hard to work w prion proteins?
aggregated; insoluble; infectious; hard to do x-ray crystallography and solution NMR
31
What do we know about prpsc strucutre?
Contain alot of beta sheet ## Footnote current strucutre is the cryo EM strucutre
32
What is PIRIBS?
PARALLEL IN-REGISTER INTERMOLECULAR BETA-SHEET STRUCUTRE; shown to make up prion structures ## Footnote Can also be four-rung beta solenoid strucutre
33
What is the prion cloud hypothesis?
Diff. conformations in diff. parts of the brain would contribute to diff. disease (major vs. minor conformations)
34
What is the refolding and seeding model for prion replication?
slide 48
35
What are the issues with immunization in prp?
1. Immunization w misfolded Prpsc would lead to disease 2. Immunization w native Prpc could be unspecific or cause autoimmune; however it would **reduce substrate conc. and delay disease** 3. Immunization w unspecific protein results in unspecific/autoimmune response
36
What are the 3 most common genetic prion dieases?
P102L (GSS); D178N (FFI); E200K (fCJD)
37