Prions Flashcards
what are the common pathologies seen in transmissible spongiform encephalopathies
multifocal spongiform changes
amyloid
astrogliosis
neuronal loss
what is the prion protein? where is it found?
209 amino acid glycoprotein that is expressed on the cell surface and is anchored ther by FA
in a single exon on chrom 20
highly expressed in NEURON and LYMPHOCYTES
nml function of PrPc
inhibit BACE1 activity which inhibits the formation of beta amyloid
differences in __ cause PrP-Sc to be ____
folding –> resistant to proteases
how does a folding difference lead to a diseased state?
aggragates form; these are unstable and cause the neuron to undergo APOPTOSIS
mice lacking ___ are resistant to prion infection. Significance?
PrP-C, meaning PrP-C is needed for the formation of PrP-Sc
**PrP-Sc forms when an intermediate of PrP-C interacts with another PrP-Sc which acts as a template for all the other abn proteins = CHAIN REACTION
what explain the late onset of sporadic CJD
PrP-C is greatly favored and it takes a long tine for the rare, pathogenic (PrP-Sc) to form (age dept mutation?)
what dictates the final conformation a prion protein assumes
template prion NOT the amino acid sequence of the protien
What is scrapie and what is its significance to human prion disease?
subacute, progressive ataxia in sheep and goats that showed transmission occurred via the alimentary tract
clinical features of Creutzfeldt-Jakob disease (CJD)
dementia, myoclonus, ataxia, akinetic mutism
most common type of CLD (sporadic, familial, or iatrogenic)
sporadic
average age of onset in sporadic and familial CLD
sporadic = 60 familial = 45 to 50
who lives longer after diagnosis, those with sporadic or familial CJD
familial (2-4 yrs vs 1 yr)
mode of inheritance for familial CJD
AD
there are specific mutations in the prion protein that appear to facilitate the conversion of C to Sc
where do spongiform changes take place with prion disease
cerebellum