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

Daniel R. Dries, Gang Yu

Research output: Contribution to journalReview article

77 Scopus citations

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 languageEnglish (US)
Pages (from-to)132-146
Number of pages15
JournalCurrent Alzheimer Research
Volume5
Issue number2
DOIs
StatePublished - Apr 1 2008

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Aph-1
  • Nicastrin
  • Pen-2
  • Presenilin
  • Protease
  • γ-secretase

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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