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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / enzymology
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / antagonists & inhibitors
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Amyloid beta-Peptides / metabolism*
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Animals
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Animals, Newborn
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Apolipoproteins E / chemistry
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Apolipoproteins E / metabolism*
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Apolipoproteins E / pharmacology
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Astrocytes / drug effects
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Astrocytes / enzymology*
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Brain / enzymology
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Brain / physiopathology
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Cells, Cultured
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Gliosis / chemically induced
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Gliosis / enzymology*
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Gliosis / physiopathology
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Inflammation Mediators / antagonists & inhibitors
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Inflammation Mediators / metabolism*
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Intracellular Signaling Peptides and Proteins / drug effects
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Intracellular Signaling Peptides and Proteins / metabolism
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Matrix Metalloproteinase 9 / drug effects
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Matrix Metalloproteinase 9 / metabolism*
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Plaque, Amyloid / metabolism
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Protein Isoforms / chemistry
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Protein Isoforms / metabolism
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Protein Isoforms / pharmacology
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Protein Serine-Threonine Kinases / drug effects
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Protein Serine-Threonine Kinases / metabolism
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Rats
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Rats, Sprague-Dawley
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rho-Associated Kinases
Substances
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Amyloid beta-Peptides
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Apolipoproteins E
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Inflammation Mediators
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Intracellular Signaling Peptides and Proteins
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Protein Isoforms
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Protein Serine-Threonine Kinases
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rho-Associated Kinases
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Matrix Metalloproteinase 9