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 Alzheimers 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 Alzheimers disease.
Keywords: Alzheimer's disease, amyloid precursor protein, Aph-1, γ-secretase, nicastrin, Pen-2, presenilin, protease
Current Alzheimer Research
Title: Assembly, Maturation, and Trafficking of the γ-Secretase Complex in Alzheimers Disease
Volume: 5 Issue: 2
Author(s): Daniel R. Dries and Gang Yu
Affiliation:
Keywords: Alzheimer's disease, amyloid precursor protein, Aph-1, γ-secretase, nicastrin, Pen-2, presenilin, protease
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 Alzheimers 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 Alzheimers disease.
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Cite this article as:
Dries R. Daniel and Yu Gang, Assembly, Maturation, and Trafficking of the γ-Secretase Complex in Alzheimers Disease, Current Alzheimer Research 2008; 5 (2) . https://dx.doi.org/10.2174/156720508783954695
DOI https://dx.doi.org/10.2174/156720508783954695 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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