Table of Contents
What is the function of gamma secretase?
gamma-Secretase catalyzes intramembrane proteolysis of various type I membrane proteins, including the amyloid-beta precursor protein and the Notch receptor. Despite its importance in the pathogenesis of Alzheimer’s disease and to normal development, this protease has eluded identification until only very recently.
What is gamma secretase made of?
γ-secretase is a high molecular weight complex minimally composed of four components: presenilins (PS), nicastrin, anterior pharynx defective 1 (APH-1), and presenilin enhancer 2 (PEN-2).
What is beta and gamma secretase?
Sequential cleavage by beta-secretase 1 (BACE) and gamma-secretase (γ-secretase) produces the amyloid-beta peptide fragment that aggregates into clumps called amyloid plaques in the brains affected by Alzheimer’s disease.
What is gamma secretase?
Gamma secretase is an internal protease that cleaves within the membrane-spanning domain of its substrate proteins, including amyloid precursor protein (APP) and Notch.
How do gamma secretase and γ-secretase interact to cleavage amyloid?
Recent research has shown that interaction of the gamma secretase complex with the γ-secretase activating protein facilitates the gamma cleavage of amyloid precursor protein into β-amyloid.
How are the proteins in the gamma secretase complex activated?
The proteins in the gamma secretase complex are heavily modified by proteolysis during assembly and maturation of the complex; a required activation step is in the autocatalytic cleavage of presenilin to N- and C-terminal fragments.
What is α-and γ-secretase?
γ-Secretase is an unusual aspartyl protease that cleaves proteins within the membrane lipid bilayer. γ-Secretase activity depends on the presence of multiple protein components including presenilin 1, which is mutated in some familial cases of Alzheimer’s disease. APP is normally processed by α- and γ-secretase to produce three peptide fragments.