prions Flashcards
Prion diseases a
rare, fatal, rapidly progressive neurodegenerative diseases that occur in humans and other animal species
histological appearance of prion disease in neuropil
Presence of small vacuoles within the neuropil, which produces a spongiform appearance
animal prion diseases
human prion diseases
Scrapie
transmissable?
fatal neurodegenerative disease of sheep
demonstrated to be a transmissible disorder
CJD
transmissable?
fatal neurodegenerative disease of humans recognized since the 1920s
demonstrated to be transmissible in the 1960s (humans to chimpanzees)
Early CJD symptoms
memory problems, behavioral changes, poor coordination, and visual disturbances
later CJD symptoms
% dead within 1 yr?
dementia, involuntary movements, blindness, weakness, and coma
70% of people die within 1 year of diagnosis
Search for agent of scrapie and CJD
infectious agents were “filterable” meaning not cellular (filters used could trap bacteria) therefore, possibly a virus
Researchers treated the infectious material to determine what it was composed of 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
protein of prion disease
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.
what encodes Prp protein
PRNP gene on chromosome 20 encodes PrP protein
Prp possible polymorphisms
Met or Val at codon 129 of PRNP gene
60% Met codon; 40% Val codon
homozygote for either = increased risk of disease
Prp degradation
resistant to degradation and accumulates in amyloid fibrils
Prp strongly expressed where? functions?
strongly expressed in both neurons and glial cells of the CNS and appears to regulate ion channels and neurotransmitter receptors at the pre- and postsynaptic levels.
CJD and variant CJD median age of death
CJD: 68
variant: 28
