4.56 Flashcards
Prion diseases are
rare, fatal, rapidly progressive neurodegenerative
diseases that occur in humans and other animal species
Prion diseases
Presence of small — within the neuropil, which produces a — appearance
vacuoles
spongiform
Neuropil:
The complex net of axonal, dendritic, and glial branchings that forms the bulk of the central nervous system gray matter of the brain and in which the nerve cell bodies are embedded
Disease: Bovine spongiform encephalopathy
Animals affected:
cattle
Disease: Scrapie
Animals affected:
sheep and goats
Human Prion Diseases (5)
Kuru
Creutzfeldt-Jakob disease (CJD)
Variant Creutzfeldt-Jakob disease (Variant CJD)
Gerstmann-Sträussler-Scheinker syndrome (GSS)
Fatal familial insomnia (FFI)
Scrapie -
fatal neurodegenerative disease of sheep
Scrapie
demonstrated to be a — disorder
transmissible
CJD -
fatal neurodegenerative disease of humans recognized since the 1920s
demonstrated to be transmissible in the 1960s (humans to chimpanzees)
CJD
Early symptoms:
memory problems, behavioral changes, poor coordination, and visual
disturbances
CJD
Later symptoms: (5)
—% of people die within 1 year of diagnosis
dementia, involuntary movements, blindness, weakness, and coma
70
Search for slow viruses that were expected to be the infectious agents of scrapie and CJD
infectious agents were “—” meaning
filterable
not cellular (filters used could trap bacteria) therefore, possibly a virus
Search for slow viruses that were expected to be the infectious agents of scrapie and CJD
Researchers treated the infectious material to determine what it was composed of (3)
ionizing radiation, which destroys DNA and RNA, did not affect transmission of scrapie and CJD
Hypothesis (1960s): scrapie and CJD are caused by infectious agents consisting solely of
proteins
The term “Prion” (2)
coined in 1982 (Stanley Prusiner; 1997 Nobel prize)
Proteinaceous, infectious
PrPSc
(=PrP folded into the prion form) recruits PrP (the non-prion form of PrP) to adopt the prion shape.
The non-prion form (“normal” form) is called
PrP or PrPC.
PRNP gene on chromosome 20 encodes
PrP protein
PrP polymorphism:
Met or Val at codon 129 of PRNP gene
60% Met codon; 40% Val codon
homozygote for either = increased risk of disease
PrPSc is resistant to — and
accumulates in —
degradation
amyloid fibrils
PrPC is strongly expressed in both (2) of the CNS and appears to regulate
neurons and glial cells
ion channels and neurotransmitter receptors at the pre- and postsynaptic levels.
Characteristic: Median age at death
CJD:
Variant CJD:
68 years
28 years
Characteristic: Median duration of illness
CJD:
Variant CJD:
4-5 months
13-14 months
Characteristic: Clinical signs and symptoms
CJD:
Variant CJD:
Dementia; early neurologic signs
Promionent psychiatric/behavioral symptoms;
painful dysthesias; delayed neurologic signs
Characteristic: Accumulation of PrPSC in brain tissue
CJD:
Variant CJD:
Variable accumulation
marked accumulation
Prions may not be inactivated by means of
routine surgical instrument sterilization
procedures.
The World health Organization and the US Centers for Disease Control and Prevention
recommend that instrumentation used in such cases be
immediately destroyed after use.
Secondary to destruction, it is recommended that (2) decontamination be
used in combination to process instruments that come in contact with high-infectivity
tissues.
heat and chemical
No cases of iatrogenic transmission of CJD have been reported subsequent to the
adoption
of current sterilization procedures, or since 1976.
