Pathology with protein folding Flashcards
Is Alzheimer’s a part of normal ageing process?
No, because there is abnormal protein folding
Why can’t abnormally folded proteins be effectively cleared?
these proteins develop postnatally, and the body is not adapted to clear these protein complexes
What are the genes involved in AD?
APP
Apolipoprotein E
PS1
PS2
Which gene is related to sporadic late onset AD?
Apo E
Where do AD normally start its effects
medial temporal and frontal lobes
What are the two principle pathologies related to AD?
NFT - neurofibriin tangle, associated with Tau
APC - formation of amyloid plaque
How are amyloid plaques formed?
APP, a transmembrane protein is cleaved by enzyme to form Ab monomers. The aggregation of monomers forms insoluble oliogomers, and eventually becomes a plaque
What is the enzyme that cleaves the APP?
y-secretase
Why can’t we target y-secretase for AD?
the enzyme cuts almost all type 1 transmembrane proteins, not just APP, so inhibiting the enzyme will inhibit many normal processes
T/F amyloid plaque doesn’t do any damage to the brain
True, it’s the Ab monomers that disrupts synaptic transmissions
The plaque is just a biomarker of AD
What kind of disease is Creutzfeldt-Jakob Disease?
prion disease
What are the symptoms of Kuru disease?
tremors and pathologic bursts of laughter
How is Kuru disease transmitted?
cannibalism
What is BSE disease also known as? Which disease is it similar to?
mad cow disease
it’s similar to kuru
How does mutation occur in BSE
At the PrP gene, the methionine at 129 (instead of valine) determines the risk of developing mutation. Mutation leads to expansion, which ultimately creates an abnormal, autosomal dominant pattern
