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27 Cards in this Set
- Front
- Back
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Transmissible Spongiform Encephalopathies are caused by ?
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An aberrant form of a constitutively expressed neuronal protein (PRION).
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What causes dementia, axtasia, insomnia, paraplegia, and parestheisa associated with spongiform encephalopathies?
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Failure to CLEAR prions.
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-amyloid plaques, atrophy, neuronal loss, vacuolation, astrocytic gliosis; non-inflammatory
-Long incubation period, then often rapidly progressive, 100% fatality rate |
Transmissible Spongiform Encephalopathies
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What is the major difference between Transmissible Spongiform Encephalopathies and Alzheimers, Parkinsons, and huntingon's?
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Transmissible Spongiform Encephalopathies are TRANSMISSIBLE!
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What are small proteins expressed primarily in neurons, and inserted into neuronal cell membranes ?
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Prions (231 aa's)
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Prions usually have short half lives and are proteolytially degraded. What is the pathogenesis of the spongiform encephalopathies?
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Aberrant forms are RESISTANT to degradation, and are non-immunogenic to host!
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What is the proposed function of prions?
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Copper binding.
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How does a normal prion turn abberant or abnormal?
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A-helix to B sheet.
-Can be genetic (inherited or spontaneous mutation: point mutation, insertion, deletion), by incorrect post-translational modification, or by “spontaneous” conversion |
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How are B sheet replicated?
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The prions are made as monomers, but then dimerize. If a beta sheet prion comes into contact with an alpha helix prion, the alpha helix prion will conform to B sheets.
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This prion dz can be inherited or somatic mutation, infection with surgical instruments, dura mater grafts, and human growth hormone. Causes PRE-SENILE DEMENTIA.
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Creutzfeld-Jacob Disease (CJD)
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Infection via prion-contaminated beef
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New variant (nvCJD)
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Inherited mutation. Progressive ataxia/dementia
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Gerstmann-Straussler-Scheinker Disease (GSS)
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Inherited mutation; rare somatic mutations, spontaneous conversions. Intractable INSOMNIA, dementia. Thalamus
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Fatal Familial Insomnia (FFI)
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Ritualistic cannibalism (Fore’ people, New Guinea)
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Kuru
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Prion disease infection via SHEEP blood, placenta.
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Scrapie
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Infection via sheep/cattle meat and bone meal
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Bovine spongiform encephalopathy (BSE)
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Captive animals. Infection via sheep/cattle meat
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Transmissible mink encephalopathy (TME)
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Initial Infection via sheep (blood) contaminated grasses. Current mechanism of spread unknown
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Chronic wasting disease (CWD, deer and elk)
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What accounts for the variety of dz caused by prions?
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Mutations @ different LOCATION in the prion gene (250 codons, chromosome 20) results in slightly different diseases!
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What is the average age of onset for CJD?
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60-65years. Bovine form is younger.
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1. Progressive vacuolation, degeneration of brain.
2. Rapidly progressive dementia and myoclonus. DEATH within year of onset. |
CJD
Bovine form: death w/in 2-3 years. |
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Prion passed to humans by ingesting beef from cattle with bovine spongiform encephalopathy (England).
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New variant (nv)CJD
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“florid” plaque
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nvCJD = vacuolization
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14-3-3 protein
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(detectable in CSF; sporadic CJD, less so/later in nvCJD) Elevated CSF tau protein.
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What blot assay would you use to detect prions in humans & animals?
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Western Blot
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“Pulvinar sign” in MRI
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nvCJD only. MRI is diagnostic.
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Treatment of prion dz?
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Quinacrine, chlorpromazine, beta sheet breaker, Ab to B sheet antigen.
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