Prions and Prion-Mediated diseases Flashcards
What lead to CJD iatrogenic transmission?
Transmission of CDJ occurred despite sterilization of instrumentation used on pts
What is the only way to destroy and prion?
Incinerate them
Where would the prion protein (PRNP) be found?
Naturally occurring CNS protein encoded by the PRNP gene
What are some characteristics of the prion protein?
Non-pathogenic Single disulfide bond N-glycosylated Attatched to plasma membrane by a C terminal PrPc largely alpha helical Structured and unstructured region
What occurs based on the Protein only hypothesis by Prusiner?
Only protein contributes to this spongiform encephalopathy
Protein misfolds and becomes PrPsc (scrapie) and accumulates plaques in brain
As they start to stack up what does PrPsc form?
Fibrils
What are the characteristics of PrPres?
Abnormal, partially protease resistant, prion disease associated isoform of PrP
Largely synonymous with PrPsc
What occurs in the autocatalytic model what seeded PrP polymerization occurs?
Confirmational converstion of PrPc to PrPres is rare unless cataluzed by contact with a pre-existing PrPres multimer
What occurs in the noncatalytic model?
Confirmational interchange between PrPc and PrPres conformations is rapid but PrPres conformer is poorly populated unless stabilized
What does PrPc do normally?
Not really known but expected to act in signal transduction primarily in neurites
What protein is similar to PrPc?
Doppel
What is amino acid 106-126?
Neurotoxic prion protein fragment
What are prions?
Proreinaceous infectious particles
How can abnormal prions occurs?
From animal to animal
Spontaneous mutation
What does the pathological form of prion do?
Binds to normal isoform, causes normal changes to abnormal confirmation
What is the main difference between normal and abnormal PrP?
Normal: Helical, degradation by proteases
Abnormal: Beta-pleated protein, resistant to degredation by proteases
In transmissible spongiform encephalopathies, what does the brain show?
Scrapie-associated fibrils
Vacuolization and atrocytosis
What are the types of spongiform encephalopathies that effect humans?
CJD Variant CJD Gerstmann-Straussler syndrome Fatal familial insomnia Kuru
How is Kuru transmitted?
Eating the brain tissue of deceased family members or open sores
What gets scrapie?
Sheep
What are the characteristics of scrapie?
Neurodegenerative disease
Caused by contact with placenta and placental fluids in infected ewes
What are the three route of acquisition of Creutzfeldt-Jacob disease (CJD)?
Sporadic
Familial
Iatrogenic (transplanted corneas, incorrect brain electrode sterilization, pituitary growth hormone injection from cadavers)
What are the clinical manifestation of CJD?
Insidious onset of psychomotor disturbances Progressive memory loss Dec cognition Myoclonus Death within months from symptom onset
Where does variant CJD come from?
Cows
How do someone acquire vCJD?
Eating infected meat from cattle infected with BSE
What id different in vCJD from CJD?
Different prion protein
Younger age onset
Sensory disturbances, psychiatric issues
Different electrical patterns
What is the proposed pathogenesis of vCJD?
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
Cross BBB
