The role of presenilin and its interacting proteins in the biogenesis of Alzheimer's beta amyloid

Giuseppe Verdile, Samuel E. Gandy, Ralph N. Martins*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

45 Citations (Scopus)


The biogenesis and accumulation of the beta amyloid protein (Aβ) is a key event in the cascade of oxidative and inflammatory processes that characterises Alzheimer's disease. The presenilins and its interacting proteins play a pivotal role in the generation of Aβ from the amyloid precursor protein (APP). In particular, three proteins (nicastrin, aph-1 and pen-2) interact with presenilins to form a large multi-subunit enzymatic complex (γ-secretase) that cleaves APP to generate Aβ. Reconstitution studies in yeast and insect cells have provided strong evidence that these four proteins are the major components of the γ-secretase enzyme. Current research is directed at elucidating the roles that each of these protein play in the function of this enzyme. In addition, a number of presenilin interacting proteins that are not components of γ-secretase play important roles in modulating Aβ production. This review will discuss the components of the γ-secretase complex and the role of presenilin interacting proteins on γ-secretase activity.

Original languageEnglish
Pages (from-to)609-623
Number of pages15
JournalNeurochemical Research
Issue number4-5
Publication statusPublished - Apr 2007
Externally publishedYes


  • Alzheimer's disease
  • Amyloid precursor protein
  • Beta amyloid
  • Gamma secretase
  • Interacting proteins
  • Presenilin


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