Genetic research on familial cases of Alzheimer disease have identified presenilin (PS) as an important membrane protein in the pathomechanism of this disease. PS is the catalytic subunit of γ-secretase, which is responsible for the generation of amyloid-β peptide deposited in the brains of Alzheimer disease patients. γ-Secretase is an atypical protease composed of four membrane proteins (i.e., presenilin, nicastrin, anterior pharynx defective-1 (Aph-1), and presenilin enhancer-2 (Pen-2)) and mediates intramembrane proteolysis. Numerous investigations have been conducted toward understanding the structural features of γ-secretase components as well as the cleavage mechanism of γ-secretase. In this review, we summarize our current understanding of the structure and activity relationship of the γ-secretase complex.
Keywords: Alzheimer disease; Intramembrane protease; Proteolysis; Structure; γ-Secretase.
Copyright © 2020 Elsevier Ltd. All rights reserved.