what are prion diseases caused by?
-not virus, bacteria, fungus or parasites
-caused by variation in conformation of normal cellular protein in CNS
-may start with into of foreign homologue from humans or other animals like cows
-can also initiate by chance or genetic predisposition
what is a prion?
proteinaceous infectious particle
-no evidence of inflammation/antibody response to infection with prions
-preclinical period lasts months to years
prions are resistant to...
what are prions sensitive to?
-protein denaturing agents
best studied prion?
causes scrapie in sheep
describe the proposed molecular disease process for prions:
-PrPsc causes molecule switch of cellular protein PrPc to the prion conformation.
-altered protein cannot be degraded by cellular proteases and accumulates in cytoplasm and extracellular areas of cells in brain
-could be caused by mutation in gene encoding for PrP protein (random or by ingesting PrPsc protein from another source)
what is PrPsc?
protease resistant prion protein
-New Guinea-transmitted by brain of dead people during prep for ritual cannibalism
Gerstmann-Straussler Scheinker Syndrome (GSS):
-prion protein mutation of P102L and others
-high prevalence found in Jewish Libyans, but found all over the world
-can be sporadic, passed via human tissue transplantation or hereditary (mutation in PrP)
-mean age of onset is 63 years
-transmission by grafts of dura mater during neurosurgery (incubation is 7years)
-3.1 pts per million people
-can occur by random misfolding of the protein
describe Fatal Familial Insomnia:
-severe atrophy of anterior, ventral and mediodorsal thalamic nuclei
-leads to insomnia and death
-most like from Bovine Spongiform Encephalopathy (animal disease)
-first in the UK
-linked to ingestion of contaminated beef
153 reported cases
-long incubation period
-related to eating British beef
-earlier onset than regular CJD (many pts in their 20s)
-early signs are irritability and memory loss and dementia (rapidly progressive), blindness, myoatrophy
-late sx-pt mute and demented and jerking often disappears
-over 80% die within 12 months of sx
-only 1 case in the US that was confirmed to have originated in the UK
which of these are genetic disorders?
CJD (not always), FFI and GSS
-causes disease in sheep
-progressive and fatal neuropathy
-loss of wool and scrape vs things to aid the process
describe bovine spongiform encephalopathy (BSE)
-progressive neuro disorder in cattle
-leads to tremors, staggering and death
-mad cow disease
-first appeared in england 1986
describe chronic wasting disease (CWD)
-deer and elk
-weight loss and neuro sx that lead to death
-concetrated to wyoming, CO and a little in michigan/new mexico
pathoogy of vCJD:
-CSF normal, no inflammation
-cerebral atrophy, neuronal loss, vacuoles in neurons with proteinaceus granules
-infected cells have fibrils resembling amyloid that consist of PrP
-note that all those diagnosed with vCJD are homozygous for methionine at position 129 of the PrP gene
incidence of position 129 of PRP gene?
how to disinfect stuff if you think CDJ or VCJD is on it?
use 1N NaOH for 1 hour and autoclave at 134 OR 2N NaOH if you can't autoclave