M10 Flashcards
What are Prion diseases?
Related group of rare, fatal brain diseases that affect animals, including humans
What is are Prion diseases also known as?
Transmissible spongiform encephalopathies (TSE)
Give some examples of Prion diseases (5)
- Mad cow disease in cattle
- Creutzfeldt-Jakob disease (CJD) in humans
- Kuru in humans
- Scrapie in sheep
- Chronic Wasting Disease in deer and elk
How do Prion diseases occur?
- Characterised by proteins that adopt alternative shapes in the brain tissues
- The prion form of the protein clumps together and accumulate in brain tissue causing damage to the brain
- These are prion forms of the protein
What are prions?
Shape shifting proteins
What is PrPC?
Where is it found?
- The normal prion protein is called PrPC
- It is a plasma membrane glycoprotein found at the cell surface
Describe the secondary structure of PrPC
Its secondary structure is dominated by alpha helixes
What is PrPSc?
How has its protein structure changed from PrPC?
- The disease-producing protein is called PrPSc (for scrapes)
- The same amino acid sequence as PrPC, but now folded with more beta-sheets
What happens when PrPSc comes into contact with PrPC?
It converts PrPC into more PrPSc
How are prion aggregates formed?
Converting PrPC into more PrPSc and these all sticking together
What are amyloid deposits?
Name a disease that involves amyloid deposits
- The deposits of PrPSc in the brain are called amyloid
- Alzheimer’s disease
What are the roles of proteasomes in cells?
Responsible for degrading misfolded or aggregated proteins
Why may proteasomes not stop prions?
- The build-up of amyloid deposits overwhelms the capacity of the proteasomes to do their job
- This leads to cell death
Name some inherited prions diseases (3)
- Creutzfeldt-Jakob Disease (CJD)
- Gerstmann-Sträussler-Scheinker disease (GSS)
- Fatal Familial Insomnia (FFI)
How can people get CJD without inheritance? (2)
- Accidental exposure to material contaminated with CJD prions (e.g surgical instruments)
- Corneal transplants have also inadvertently transmitted CJD
What is Gerstmann- Sträussler- Scheinker disease (GSS) caused by? (2)
- Inheritance of a PRNP gene containing mutations
- Transgenic mice expressing the P102L gene develop the disease spontaneously
What is Fatal Familial Insomnia (FFI) caused by? (2)
Inherited a PRNP gene with asparagine instead of aspartic acid encoded at position 178 (D178N)
What are the 4 stages of Fatal Familial Insomnia (FFI)?
- Stage 1: Insomnia, panic attacks, phobias
- Stage 2: Hallucinations, panic attacks
- Stage 3: Complete Inability to sleep, rapid weight
loss, early menopause, impotence. - Stage 4: Dementia and Death
Give some examples of infectious prion diseases (4)
- Kuru
- Scrapie
- Variant Creutzfeldt-Jakob Disease (vCJD)
- Miscellaneous Infectious Prion Diseases
How can scrapies be transmitted? (2)
- Animal to animal
- Injection of brain tissue
How does kuru disease occur?
Eating brain tissue
What are the 3 stages of Kuru disease?
- 1st stage: Unsteadiness, clumsiness, eye tremors, slurred speech.
- 2nd stage: not able to walk without help, severe tremors, muscle jerking, loss of coordination, laughter outbursts, slurred speech.
- Terminal stage: unable to sit up, tremors, incontinence, difficulty swallowing and death.
What is another name for mad cow disease?
Bovine Spongiform Encephalopathy (BSE)
How did mad cow disease arise?
Its origin appears to have been cattle feed that contained brain tissue from sheep infected with scrapie
Describe the genealogy involved in Variant Creutzfeldt-Jakob Disease (vCJD)?
All the patients are homozygous for the susceptibility polymorphism of methionine at position 129
How was mad cow disease combatted?
Ban on the use of bovine offal in baby foods
What are some clinical and pathological features of vCJD? (3)
- An early age of onset or death
- A prolonged duration of illness
- A predominantly psychiatric presentation including anxiety, depression, withdrawal behavioural change which progresses
What are some control measures for prion diseases (3)
- Recipients of Blood transfusions or blood products cannot be blood donors.
- Use of disposables in surgical procedures
- Cell lines banked post 1980 in the UK are generally not
used for the production of vaccines or biotherapeutics
