Gamma-secretase regulates VEGFR-1 signalling in vascular endothelium and RPE

Adv Exp Med Biol. 2008:613:313-9. doi: 10.1007/978-0-387-74904-4_36.

Abstract

In conclusion, gamma-secretase is expressed in both retinal microvascular endothelial cells and RPE cells and is able to elicit regulated intramembrane proteolysis of VEGFR1. Furthermore, gamma-secretase regulates the translocation of the intracellular domain of VEGFR1 as well as full length VEGFR1 in both cell types. Gamma-secretase is clearly able to act as a potent negative regulators of VEGFR2 induced in vitro angiogenesis but its role in the RPE has yet to be elucidated. We conclude that gamma-secretase may offer a therapeutic target for the treatment of both retinal and choroidal neovascularization.

Publication types

  • Review

MeSH terms

  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism*
  • Animals
  • Capillary Permeability / physiology
  • Endothelium, Vascular / metabolism*
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Hydrolysis
  • Ligands
  • Neovascularization, Pathologic / pathology
  • Pigment Epithelium of Eye / metabolism*
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Signal Transduction*
  • Vascular Endothelial Growth Factor Receptor-1 / chemistry
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*

Substances

  • Ligands
  • Protein Isoforms
  • Vascular Endothelial Growth Factor Receptor-1
  • Amyloid Precursor Protein Secretases