Lecture 37 Flashcards
Amyloid plaques stained for PrPSc or spongiform vacuoles seen at autopsy Plaques are seen in? Spongiform vacuoles seen in?
Plaques: kuru and vCJD Spongiform vacuoles: CJD
Because conventional slow viral diseases are given as distractors in questions about prion diseases, what do you need to distinguish the prion from distractors?
Presence of either DNA or RNA
Compare and Contrast between PrPc and PrPSc
The are almost identical in protein sequence and differ only in their tertiary structure due to folding PrPSc found intracellularly, PrPC on cell surface
Compare the genetic mutation of CJD and FFI
Result of 2 combined mutations in PRNP gene 1. Must have aspartic acid to asparagine mutation at codon 178 2. Second mutation at codon 129 dictates disease: Valine = CJD Methionine = FFI paste-41940355645443.jpg
Describe characteristics of PrPSc Resistance?
Aggregates of protease-resistant, hydrophobic glycoprotein Resistant to formaldehyde, UV, Heat Contains Beta-pleated sheet that is not prone to changes
Describe the characteristics of cellular prion protein (PrPC)
Located on Chromosome 20 Protease sensitive Contains alpha helix that is prone to changes
Describe the method of transmission for Creutzfeldt-Jakob Disease (CJD)
Transmitted by exposure to infected brain material: 1. Injection (Human growth hormone) 2. Transplantation (ex. dura mater graft) 3. Contaminated medical devices (brain electrodes) 4. Food Usually affects people older 50 years old
Describe the pathogenesis of unconventional slow viruses
- Caused by prions (Mutant form of a host protein) Prion stands for proteinaceous infectious particle 2. Cause spongiform encephalopathies (slow neurodegenerative diseases with long incubation) 3. Do not conform to definition of a virus - No virion structure or genome - No immune response - Extremely resistant to inactivation
Describe: Fatal familial insomnia (FFI) what causes it who is prone symptoms?
Genetic mutations Wide age range of onset Symtoms for 6-30 months with inability to sleep myoclonus, ataxia, dementia Spongiform degeneration may not always occur
Describe: Gerstmann-Straussler-Scheinker syndrome (GSS)
Rare subset of inherited form of CJD with earlier onset
Describet the details of the Prion Theory
- PrPSc binds to normal PrPC on cell surface, causing it to refold and acquire the structure of PrPSc 2. Prion protein appears to “self-replicate” by converting additional molecules of PrPC to PrPSc (cause refolding 3. PrPSc released from cell; aggregates as amyloid-like plaques in the brain 4. Accumulation causes neurodegenerative disease 5. Cell then replenishes PrPC, and cycle continues
Diagnosis of prion disease
Initial diagnosis made on clinical grounds: - No direct methods to detect prions in tissue - No serologic tests available - Confirmation by detecting proteinase K-resistant PrPSc in a Western blot Amyloid plaques stained for PrPSc or spongiform vacuoles seen at autopsy
Name the four animal diseases from unconventional viral diseases
- Scrapie 2. Bovine spongiform encephalopathy (BSE); Mad cow disease Associated with new variant CJD 3. Chronic wasting disease (in mule deer and elk) 4. Transmissible mink encephalopathy
Name the four conventional agents that cause slow diseases and what they cause
- Measles: Subacute sclerosing panencephalitis (SSP) 2. Papovavirus JC: Progressive multifocal leukoencephalopathy 3. Rubella: Chronic rubella panencephalitis 4. AIDS: HIV
Name the four human diseases from unconventional viral diseases
- Kuru 2. Creutzfeldt-Jakob disease (CJD) 3. Gerstmann-Straussler-Scheinker (GSS) syndrome 4. Fatal Familial Insomnia (FFI)
