Presenilin diversifies its portfolio

Trends Genet. 2007 Mar;23(3):140-50. doi: 10.1016/j.tig.2007.01.008. Epub 2007 Feb 5.


Presenilin, the catalytic member of the gamma-secretase proteolytic complex, was discovered through its roles in generating Alzheimer's-disease-associated amyloid-beta peptides from the amyloid-beta precursor protein and in releasing the transcriptionally active domain of the receptor Notch. Recent work has revealed many additional cleavage substrates and interacting proteins, suggesting a diversity of roles for presenilin during development and adult life, some of which might contribute to Alzheimer's disease progression. Although many of these functions depend on the proteolytic activity of gamma-secretase, others are independent of its role as a protease. Here, we review recent data on candidate functions for presenilin and its interactors and on their potential significance in disease.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism
  • Calcium / metabolism
  • Cell Adhesion
  • Humans
  • Nerve Tissue Proteins / metabolism
  • Phosphorylation
  • Presenilins / metabolism
  • Presenilins / physiology*
  • Signal Transduction*
  • Substrate Specificity
  • Transcription, Genetic
  • tau Proteins / metabolism


  • Nerve Tissue Proteins
  • Presenilins
  • tau Proteins
  • Amyloid Precursor Protein Secretases
  • Calcium