Abstract
In this review, we discuss the biology of γ-secretase, an enigmatic enzyme complex that is responsible for the generation of the amyloid-β peptide that constitutes the amyloid plaques of Alzheimer's disease. We begin with a brief review on the processing of the amyloid precursor protein and a brief discussion on the family of enzymes involved in regulated intramembrane proteolysis, of which γ-secretase is a member. We then identify the four major components of the γ-secretase complex - presenilin, nicastrin, Aph-1, and Pen-2 - with a focus on the identification of each and the role that each plays in the maturation and activity of the complex. We also discuss two new proteins that may play a role in modulating the assembly and activity of the γ-secretase complex. Next, we summarize the known subcellular locations of each γ-secretase component and the sites of γ-secretase activity, as defined by the production of Aβ. Finally, we close by synthesizing all of the included topics into an overarching model for the assembly and trafficking of the γ-secretase complex, which serves as a launching point for further questions into the biology and function of γ-secretase in Alzheimer's disease.
Original language | English (US) |
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Pages (from-to) | 132-146 |
Number of pages | 15 |
Journal | Current Alzheimer research |
Volume | 5 |
Issue number | 2 |
DOIs | |
State | Published - Apr 2008 |
Keywords
- Alzheimer's disease
- Amyloid precursor protein
- Aph-1
- Nicastrin
- Pen-2
- Presenilin
- Protease
- γ-secretase
ASJC Scopus subject areas
- Neurology
- Clinical Neurology