Prions Flashcards
What are TSE’s ?
Transmissible Spongiform Encephalopothy-a family of rare progressive neurodegenerative disorders that affect both humans and animals.
How are TSE’s distinguished?
- long incubation periods,
- characteristic spongiform changes
- neuronal loss,
- failure to induce inflammatory response
What are the most common TSE diseases?
- Creutzfeldt-Jakob
- Variant Creutzfeldt Jakob
- Mad-Cow
- Gerstmann-Straussler Scheinker syndrome
- Fatal Familial insomnia
- Kuru
What is the normal prion in the human body?
Cellular prion protein PrPC
What codes for the normal prion protein?
the PRNP gene
What is the abnormal prion protein?
PrPSc
How is the abnormal prion protein created?
PrPC undergoes a conformational change to the abnormal PrPSc
How does this abnormal prion protein cause disease?
PrPSc is insoluble and initiates an autocatalytic reaction leading to the accumulation of amyloid (protein) in the CNS which via unknown mechanisms leads to neurodegeneration
What are the 3 forms of Creutzfeldt-Jakob Disease?
- Sporadic
- Hereditary
- Acquired
What are the signs and symptoms of CJD?
- abnormal shaking/jerking movements,
- rapid mental deterioration * dementia with seizures,
- previous dural implants
- human growth hormone treatment.
What is CJD resistant to?
- formalin fixation
* paraffin embedding.
When does CJD usually manifest?
60s, death within 6 months
How can CJD be transmitted?
- dural implants,
- contaminated pituitary growth hormone,
- cornea tranplants.
What are ways to inactivate CJD?
- Incineration at 1000 degrees C
- Autoclaving at 134 degrees C for 20 minutes
- Bleach for one hour
What commo methods of inactivation do not work on CJD?
- Ammonia
- Formaldehyde fixation
- Autoclaving at 121 degrees C
What are the differences between CJD and vCJD?
- The median age of death for vCJD is 28 years old
* Prominent psychiatric and sensory symptoms (vCJD)
What causes Kuru?
Cannibalism in the indigenous people of New Guinea and ingesting prion infected brains
What are signs/symptoms of Fatal Familial Insomnia?
- Sleep disturbances,
- muscle spasms,
- stiffness,
- eventually mental deterioration.
What causes Fatal Familial Insomnia?
- Genetic defect in PRNP gene coding for PrPc
- Almost all cases are inherited
- Autosomal dominant pattern.
What scan can identify Fatal Familial Insomnia?
PET scan may detect abnormalities
What are the signs/symptoms of Gertsmann-Straussler-Scheinker?
- Prion disease exhibits loss of coordination
- slowly delayed mental dysfunction.
- deterioration of the cerebellum responsible for muscle tone and coordination, balance
Is Gertsmann-Straussler-Scheinker inherited or acquired?
- Autosomal Dominant disorder (mutations in PRNP gene)
* though some cases are sporadic (NIH).
Can CWD be transmitted to humans?
No documented cases currently exist
