Gamma Secretase
Introduction
5A63 Article
Background
Gamma Secretase is a transmembrane aspartate protease
Catalyzes peptide bond hydrolysis of type I integral membrane proteins
Such as Notch, APP, and various other substrates
3 residue segments; allow binding and cleavage
Generates amyloid-β (Aβ)
Important for neural processes
Implications with Alzheimer’s disease (AD)
Drug target
GS inhibitors
Dangerous side effects
practice
Structural highlights
Relevance and Disease
APP build up leads to Amyloid plaques in brain
Inhibition of γ-secretase could be potential AD treatment
Location of majority of mutations
Over 200 mutations that cause AD
AD mutations heavily target interface between PS1 and APP
Important to look at differences between substrates
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