Prion diseases:

History:
- Proteins were described as distinct biological molecules and their cellular significance in
cellular processes as early as 18th century
- Around this time= earliest reported cases of this about sheep= scarping against fences=
where the “scrapie” name came from
- In late 19th century=Koch talked about causative agents of this disease
- In 20th century= pathologist Creutzfeldt & Jakob described the disease as transmissible
spongiform encephalopathies (TSE)
- Dr. Stanley Prusiner= coined the term prion= proteinaceous infectious particles
- Now we know many prion diseases that’s due to these abnormal prion proteins
Prion diseases:
- Bovine Spongiform Encephalopathy (BSE) = mad cow disease
- Chronic wasting Disease (CWD)= elk, moose, deer
- Scrapie= sheep
- Transmissible mink encephalopathy=
- Feline spongiform encephalopathy
- Ungulate spongiform encephalopathy= exotic zoo animals
Prions:
- Normal protein that exists in neurons mainly in the brain & CNS
- Mainly made w/ alpha helices
- Function= unknown but suspected to be role in synapses between neurons in uptake of
Cu into cell, antioxidant activity & prevent neuronal dysfunction
Mechanism of prion disease:
- Due to the abnormal version of a normal protein in out body
- Alpha to beta sheets= changes solubility and properties of the normal protein
- Act as a template= when one forms can form others to form the infectious protein
- Amyloid fibers= formed by normally soluble proteins, which assemble to form insoluble
fibers that are resistant to degradation= Accumulation of these insoluble fibrous protein
aggregates, called amyloids
Prpc vs prpSc
- Prpc= soluble, can be degraded by proteinase K, monomer, not infectious
- prpSc= non soluble= stays there, can’t be degraded by PK, multimeric or aggregate
Transmission:
- sporadic= spontaneous misfolding of protein= no unknown causes
- inherited= mutations in the PRNP gene
- acquired= through contaminated meat or iatrogenic processes =contaminated meat of
cows, sheep mainly and iatrogenic as in medical procedures and these not sterilized
properly = cornea transplantation

CJD:
- cause degeneration of cerebral cortex & cerebellum
pathogenesis:
- how the disease dev.
vCJD:
- cow= Bovine spongiform encephalopathy= mad cow disease
- sheep= scrapie
- Enter neurons by adsorptive endocytosis = PM nerve cells inward to let molecules
which can’t cross the membrane
Fatal familial insomnia
- - sleep gate for nonrapid eye movement sleep is a thalamic function but it is assisted by
melatonin which acts by promoting spindle formation. Thus, melatonin has a modulatory
influence on sleep onset and maintenance.
Symptoms:
- Asymptomatic for decades but once dev. Causes death within a year
- Myoclonus= quick jerky movement of muscles
Diagnosis:
- Lumbar for 14-3-3- protein= apoptosis of neurons=significant neuronal destructions
- - prevent blood transfusion, sterilizing contaminated surgical instruments
- - Since no cure= best is to prevent transmission