CAS BI 525 Lecture Notes - Lecture 33: Biotinylation, Adam10, Gamma Secretase
17 Dec 2016
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Document Summary
Gamma and alpha-secretase in ad: alpha-secretase cleaves x in the transmembrane domain and keeps abeta from being made, beta-secretase cleaves c99 into abeta. However, ps1 will keep it from making abeta: major challenges of targeting ps1. Gamma-secretases has a lot of functions: notch-signal transduction pathway. Notch is cleaved by alpha-secretase at the plasma membrane then gamma- secretase (after endocytosis) which results in the nicd that travels to nucleus to regulate genes that control development. No gamma-secretase no icd produced, no developmental genes produced: role of nicastrin (in gamma-secretase) C99 us recognized by nicastrin and recruited within the presenlin complex, cleaved within the substrate. Sheddase any enzyme that prepares the substrate to be recognized by nicastrin. Could also be notch or other substrates. Possible intervention: cap the c99 terminal but not notch: gamma-secretase cleavage of abeta. Iacd n-terminal of this cleavage; can go to nucleus and change transcription. Iacd is the final product of both pathways.
