CAS NE 525 Lecture Notes - Lecture 15: Synaptic Plasticity, Neprilysin, Genetically Modified Organism
10 Aug 2018
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Document Summary
Amyloid beta plaques (extracellular): pathway through app cleaved by beta and gamma secretases that release abeta. Oligomer is smaller aggregation of proteins that precedes plaque just molecules of abeta. B-amyloid plaque: different from amyloid, beta amyloid contains specifically b-amyloid peptide deriving from app (ab40, ab42) Generated by amyloidogenic processing pathway misfolds into beta sheet when released from app, makes peptide prone to aggregation: b-amyloid peptides forms oligomers that are toxic and will further aggregate into fibrils, forming core of plaque. The size/number of plaques increases following the progression of the disease. App cleaves by two secratases: beta secretase cleaves at beginning of sequence for abeta within app protein, gamma secretase cleaves at end, cannot be cleavage by gamma secretase on full length app, beta secretase must cleave before. Formation of oligomers eventually organizes into protofibrils and then into amyloid. 4 kilodaltons as average molecular weight for ab40 or ab42 difficult to detect by western blot (very small)
