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
what diagnostic fining is specific to CLD
periodic complexes on EEG
clinical features of GSS dz
gait abn and ataxia
DEMENTIA IS LESS COMMON
etiology of GSS
mutation at codon 102 of prion protein and has AD pattern of inheritence
clinical features of FFI
sleep disturbances and autonomic dysfunction
etiology of FFI
mutation in codons 129 and 178 with AD pattern of inheritance
vCJD is the same dz as
mad cow (aka BSE)
etiology of vCJD
consuption of contaminated beef (also blood transfusions noted)
sources of iatrogenic CJD
dural and corneal grafts
pituitary derived hGH
avg age on onset for vCJD
29!!! VERY YOUNG (younger than familial/genetic etiologies= familial CJD, FFI, GSS)
clinical characteristics of vCJD
anxiety, depression, visual problems
all pts with vCLD had what gene polymorphism in common
homologous for menthionine at codon 129 of PrP
histo changes unique to vCJD
florid plaques and spingiform changes in BASAL GANGLIA
subcellular location of PrPc vs PrPSc
C = cell surface and Sc = intracellular vesicles
which prion diseases are assc with plaques?
GSS and vCJD
which prion diseases are assc with cerebellar spongiform changes
CJD, GSS
*vCJD are in basal ganglia
