The role of macrophage migration inhibitory factor in Alzheimer's disease

Previous studies have shown that amyloid beta protein (Abeta ), the essential molecule for the formation of toxic oligomers and, subsequently, Alzheimer plaques, has been associated in vivo with the immune modulator, macrophage migration inhibitory factor (MIF) (17). To further investigate this asso...

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Veröffentlicht in:Molecular medicine (Cambridge, Mass.) Mass.), 2010-03, Vol.16 (3-4), p.116-121
Hauptverfasser: Bacher, Michael, Deuster, Oliver, Aljabari, Bayan, Egensperger, Rupert, Neff, Frauke, Jessen, Frank, Popp, Julius, Noelker, Carmen, Reese, Jens Peter, Al-Abed, Yousef, Dodel, Richard
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container_issue 3-4
container_start_page 116
container_title Molecular medicine (Cambridge, Mass.)
container_volume 16
creator Bacher, Michael
Deuster, Oliver
Aljabari, Bayan
Egensperger, Rupert
Neff, Frauke
Jessen, Frank
Popp, Julius
Noelker, Carmen
Reese, Jens Peter
Al-Abed, Yousef
Dodel, Richard
description Previous studies have shown that amyloid beta protein (Abeta ), the essential molecule for the formation of toxic oligomers and, subsequently, Alzheimer plaques, has been associated in vivo with the immune modulator, macrophage migration inhibitory factor (MIF) (17). To further investigate this association in vivo we used the APP transgenic mouse model. Serial brain sections of transgenic APP mice were stained for Abeta plaques and MIF and we observed MIF immunolabeling in microglial cells in association with Abeta plaques in the transgenic mouse brain sections. In addition, functional studies in murine and human neuronal cell lines revealed that Abeta-induced toxicity could be reversed significantly by a small molecule inhibitor of MIF (ISO-1). Finally, to elucidate the role of MIF in Alzheimer's Disease (AD) we measured MIF levels in the brain cytosol and cerebrospinal fluid (CSF) of AD patients and age-matched controls. Our results demonstrate a marked increase of MIF levels within the CSF of AD patients compared with controls. Combined, our results indicate a strong role for MIF in the pathogenesis of AD and furthermore suggest that inhibition of MIF may provide a valuable avenue of investigation for the prevention of disease onset, progression and/or severity.
doi_str_mv 10.2119/molmed.2009.00123
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subjects Aged
Alzheimer Disease - cerebrospinal fluid
Alzheimer Disease - metabolism
Amyloid beta-Peptides - metabolism
Amyloid beta-Protein Precursor - genetics
Analysis of Variance
Animals
Brain - metabolism
Brain Chemistry
Cell Survival - drug effects
Female
Histocytochemistry
Humans
Intramolecular Oxidoreductases - antagonists & inhibitors
Intramolecular Oxidoreductases - cerebrospinal fluid
Intramolecular Oxidoreductases - metabolism
Isoxazoles - pharmacology
Macrophage Migration-Inhibitory Factors - antagonists & inhibitors
Macrophage Migration-Inhibitory Factors - cerebrospinal fluid
Macrophage Migration-Inhibitory Factors - metabolism
Male
Mice
Mice, Transgenic
Neuroblastoma
Protease Nexins
Receptors, Cell Surface - genetics
Statistics, Nonparametric
Tumor Cells, Cultured
title The role of macrophage migration inhibitory factor in Alzheimer's disease
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