Effects of apoE isoforms on beta-amyloid-induced matrix metalloproteinase-9 in rat astrocytes

Brain Res. 2006 Sep 21;1111(1):222-6. doi: 10.1016/j.brainres.2006.06.041. Epub 2006 Aug 17.

Abstract

Matrix metalloproteinase-9 (MMP-9) may play a role in the inflammatory glial response during Alzheimer's disease (AD). Astrocytes can degrade beta-amyloid (Abeta) and extracellular proteolysis via MMP-9 may be involved. Because Apolipoprotein E (APOE) genotype is an important factor for AD, we ask whether various apoE isoforms can influence Abeta-induced MMP-9 responses in primary rat astrocytes. Our data show that apoE4 significantly dampens Abeta-induced MMP-9 levels, possibly by downregulating the Rho-Rho kinase (ROCK) pathway. Reduction of astrocytic MMP-9 by apoE4 may affect Abeta clearance and promote Abeta deposition in AD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / enzymology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Animals, Newborn
  • Apolipoproteins E / chemistry
  • Apolipoproteins E / metabolism*
  • Apolipoproteins E / pharmacology
  • Astrocytes / drug effects
  • Astrocytes / enzymology*
  • Brain / enzymology
  • Brain / physiopathology
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Gliosis / chemically induced
  • Gliosis / enzymology*
  • Gliosis / physiopathology
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism*
  • Intracellular Signaling Peptides and Proteins / drug effects
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / metabolism*
  • Plaque, Amyloid / metabolism
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Isoforms / pharmacology
  • Protein-Serine-Threonine Kinases / drug effects
  • Protein-Serine-Threonine Kinases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • rho-Associated Kinases

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Inflammation Mediators
  • Intracellular Signaling Peptides and Proteins
  • Protein Isoforms
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • Matrix Metalloproteinase 9