title: Membrane trafficking and proteolytic activity of γ-secretase in Alzheimer's disease.
abstract: γ-Secretase is an intramembrane-cleaving protease that generates various forms of amyloid-β peptides (Aβ) that accumulate in the brains of Alzheimer's disease (AD) patients. The intracellular trafficking and subcellular localization of γ-secretase are linked to both qualitative and quantitative changes in Aβ production. However, the precise intracellular localization of γ-secretase as well as its detailed regulatory mechanisms have remained elusive. Recent genetic studies on AD provide ample evidence that alteration of the subcellular localization of γ-secretase contributes to the pathogenesis of AD. Here we review our current understanding of the intracellular membrane trafficking of γ-secretase, the association between its localization and proteolytic activity, and the possibility of γ-secretase as a therapeutic target against AD.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kanatsu
authors.forename: Taisuke
authors.identifier: 0000-0002-0075-5943
authors.initials: T
authors.lastname: Tomita
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport; D059748:Proteolysis
chemical_list: D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases