Prions and Prion-Mediated diseases

Question 1

What lead to CJD iatrogenic transmission?

Answer 1

Transmission of CDJ occurred despite sterilization of instrumentation used on pts

Question 2

What is the only way to destroy and prion?

Answer 2

Incinerate them

Question 3

Where would the prion protein (PRNP) be found?

Answer 3

Naturally occurring CNS protein encoded by the PRNP gene

Question 4

What are some characteristics of the prion protein?

Answer 4

Non-pathogenic
Single disulfide bond
N-glycosylated 
Attatched to plasma membrane by a C terminal 
PrPc largely alpha helical
Structured and unstructured region

Question 5

What occurs based on the Protein only hypothesis by Prusiner?

Answer 5

Only protein contributes to this spongiform encephalopathy

Protein misfolds and becomes PrPsc (scrapie) and accumulates plaques in brain

Question 6

As they start to stack up what does PrPsc form?

Answer 6

Fibrils

Question 7

What are the characteristics of PrPres?

Answer 7

Abnormal, partially protease resistant, prion disease associated isoform of PrP
Largely synonymous with PrPsc

Question 8

What occurs in the autocatalytic model what seeded PrP polymerization occurs?

Answer 8

Confirmational converstion of PrPc to PrPres is rare unless cataluzed by contact with a pre-existing PrPres multimer

Question 9

What occurs in the noncatalytic model?

Answer 9

Confirmational interchange between PrPc and PrPres conformations is rapid but PrPres conformer is poorly populated unless stabilized

Question 10

What does PrPc do normally?

Answer 10

Not really known but expected to act in signal transduction primarily in neurites

Question 11

What protein is similar to PrPc?

Answer 11

Doppel

Question 12

What is amino acid 106-126?

Answer 12

Neurotoxic prion protein fragment

Question 13

What are prions?

Answer 13

Proreinaceous infectious particles

Question 14

How can abnormal prions occurs?

Answer 14

From animal to animal

Spontaneous mutation

Question 15

What does the pathological form of prion do?

Answer 15

Binds to normal isoform, causes normal changes to abnormal confirmation

Question 16

What is the main difference between normal and abnormal PrP?

Answer 16

Normal: Helical, degradation by proteases
Abnormal: Beta-pleated protein, resistant to degredation by proteases

Question 17

In transmissible spongiform encephalopathies, what does the brain show?

Answer 17

Scrapie-associated fibrils

Vacuolization and atrocytosis

Question 18

What are the types of spongiform encephalopathies that effect humans?

Answer 18

CJD
Variant CJD
Gerstmann-Straussler syndrome
Fatal familial insomnia
Kuru

Question 19

How is Kuru transmitted?

Answer 19

Eating the brain tissue of deceased family members or open sores

Question 20

What gets scrapie?

Answer 20

Sheep

Question 21

What are the characteristics of scrapie?

Answer 21

Neurodegenerative disease

Caused by contact with placenta and placental fluids in infected ewes

Question 22

What are the three route of acquisition of Creutzfeldt-Jacob disease (CJD)?

Answer 22

Sporadic
Familial
Iatrogenic (transplanted corneas, incorrect brain electrode sterilization, pituitary growth hormone injection from cadavers)

Question 23

What are the clinical manifestation of CJD?

Answer 23

Insidious onset of psychomotor disturbances 
Progressive memory loss
Dec cognition
Myoclonus 
Death within months from symptom onset

Question 24

Where does variant CJD come from?

Answer 24

Cows

Question 25

How do someone acquire vCJD?

Answer 25

Eating infected meat from cattle infected with BSE

Question 26

What id different in vCJD from CJD?

Answer 26

Different prion protein
Younger age onset
Sensory disturbances, psychiatric issues
Different electrical patterns

Question 27

What is the proposed pathogenesis of vCJD?

Answer 27

Orally ingested prions absorbed and transported to blood and lymph fluid
Peripheral replication in the spleen, tonsils or other lymph tissue
Prions transported to brain by peripheral nerves
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