Format

Send to:

Choose Destination
See comment in PubMed Commons below
Curr Alzheimer Res. 2008 Apr;5(2):132-46.

Assembly, maturation, and trafficking of the gamma-secretase complex in Alzheimer's disease.

Author information

  • 1Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA. Daniel.Dries@UTSouthwestern.edu

Abstract

In this review, we discuss the biology of gamma-secretase, an enigmatic enzyme complex that is responsible for the generation of the amyloid-beta 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 gamma-secretase is a member. We then identify the four major components of the gamma-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 gamma-secretase complex. Next, we summarize the known subcellular locations of each gamma-secretase component and the sites of gamma-secretase activity, as defined by the production of Abeta. Finally, we close by synthesizing all of the included topics into an overarching model for the assembly and trafficking of the gamma-secretase complex, which serves as a launching point for further questions into the biology and function of gamma-secretase in Alzheimer's disease.

PMID:
18393798
[PubMed - indexed for MEDLINE]
PMCID:
PMC2474811
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Bentham Science Publishers Ltd. Icon for PubMed Central
    Loading ...
    Write to the Help Desk