Gamma-secretase and the intramembrane proteolysis of Notch

Curr Top Dev Biol. 2010;92:201-30. doi: 10.1016/S0070-2153(10)92006-1.


Gamma-secretase is the crucial proteolytic activity that releases the Notch intracellular domain and is therefore a central player in the canonical Notch-signaling transduction pathway. We discuss here briefly the discovery of gamma-secretase and what is known on its structure and function. Recent work also indicates that the assembly and activity of gamma-secretase might be regulated by novel cell biological mechanisms. Finally we explore the recent insight that there are several gamma-secretase complexes in mammalian and discuss possibilities to use gamma-secretase as a drug target in Alzheimer's disease and cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / therapy
  • Amyloid Precursor Protein Secretases / chemistry*
  • Amyloid Precursor Protein Secretases / physiology*
  • Animals
  • Humans
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Protein Processing, Post-Translational*
  • Receptors, Notch / antagonists & inhibitors
  • Receptors, Notch / metabolism*
  • Signal Transduction*


  • Receptors, Notch
  • Amyloid Precursor Protein Secretases