Prion Diseases Flashcards
What are some of the clinical manifestations of prion diseases?
Dementia
Ataxia
Insomnia
Paraplegia
Paraesthesias (tingling or burning sensations)
Deviant behaviour
What is unique about prion diseases?
The only example of an infectious agent with no nucleic acid (DNA or RNA)
How can prion diseases manifest?
As infectious, genetic or sporadic disorders
No other group has such a wide spectrum of manifestations
What is the origin point of prion diseases?
They result from an accumulation of PrP sc, which has a substantially different conformation to its normal precursor PrPc
Why are there different types of prion disease?
PrPsc can have many different conformations, each of which is associated with a specific disease
What is the structure of PrPc?
3 alpha helixes and 2 short beta strands
What is the structure of PrPsc?
It may only have 2 alpha helixes and more beta strands
What is template directed misfolding?
When the mutant form binds to normal prion protein molecules in nerve cells and causes them to permanently misfold
What distinguishes prions from viruses?
PrPsc is encoded for by a chromosomal gene
Is there a function for PrPc?
It is uncertain as PrPc knockout in mice shows no obvious abnormalities
What happens due to proteolysis of PrPsc?
It produces smaller protease resistant molecules of approximately 142 amino acids, designated PrP 27-30. Which polymerise into amyloid
Describe sporadic creutzfeldt Jakob disease
It is characterised by vacuolation of the neurophil in the gray matter by exuberant reactive astrocytic gliolis
Determined by the degree of nerve cell loss
What is distinguishing about the new variant of creutzfeldt Jakob disease?
The abundance of PrO amyloid plaques, which are often surrounded by a hall of intense vacuolation
What is seeded aggregation?
The process whereby misfolded proteins recruit and initiate template directed misfolding of the native protein to form new aggregates
What is astrogliosis?
The proliferation of astrocytes to fill up empty space
