Amyloid B-peptide Flashcards
What is the precursor to Ab?
APP - Amyloid Precursor Protein
What is the first stage in the creation of Ab from APP?
Cleavage by B-secretase, which releases a large secreted derivative, aAPPb and CTFb
What is sAPPb?
One of the products of the cleavage of APP by b-secretase
What is CTFb?
A 99-amino acid fragment which begins with the N-terminal aspartyl residue of Ab, it remains membrane bound
What is the second stage in the creation of Ab from APP?
Cleavage of CTFb by y-secretase, which produces Ab
What does y-secretase do?
Cleave CTFb into Ab
What is notable about the cleavage by y-secretase?
It is imprecise and results in a c-terminal heterogeneity of the resulting peptide population, leaving numerous Ab species in existence.
What Ab species end up in existance and in what percentages?
Ab40 (cleaved to end at position 40) at 80-90% and Ab42 at 5-10%
What is special about Ab42?
Longer chains, so more hydrophobic and fibrillogenic, and the principle species deposited in the brain.
Which is the rate limiting step of the production of Ab?
The b-secretase step
What percentage of the total APP does b-secretase process?
~10%
What processes the remaining 90% of the APP?
alpha-secretase, a collection of metalloprotease enzymes
What does alpha-secretase do?
generates sAPPalpha and the 83 amino acid fragment CFTalpha
What does y-secretase cleavage of CFTalpha produce?
the benign p3 fragment instead of Ab
