Effects of apoE isoforms on beta-amyloid-induced matrix metalloproteinase-9 in rat astrocytes.
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.
Guo
Shuzhen
S
Department of Neurology, Mass General Hospital, Charlestown, MA, USA.
Wang
Sophia
S
Kim
Woo Jean
WJ
Lee
Sun-Ryung
SR
Frosch
Matthew P
MP
Bacskai
Brian J
BJ
Greenberg
Steven M
SM
Lo
Eng H
EH
D000544:Alzheimer Disease / Q000201:enzymology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001057:Apolipoproteins E / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D001921:Brain / Q000201:enzymology / Q000503:physiopathology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005911:Gliosis / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020780:Matrix Metalloproteinase 9