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 |
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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. |
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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.</description><identifier>ISSN: 1076-1551</identifier><identifier>EISSN: 1528-3658</identifier><identifier>DOI: 10.2119/molmed.2009.00123</identifier><identifier>PMID: 20200619</identifier><language>eng</language><publisher>England: ScholarOne</publisher><subject>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</subject><ispartof>Molecular medicine (Cambridge, Mass.), 2010-03, Vol.16 (3-4), p.116-121</ispartof><rights>Copyright 2010, The Feinstein Institute for Medical Research 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-b958fa1353c619d17f0400f622abc63db35251aae695246e418b99c16c5e84e93</citedby><cites>FETCH-LOGICAL-c464t-b958fa1353c619d17f0400f622abc63db35251aae695246e418b99c16c5e84e93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829616/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829616/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20200619$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bacher, Michael</creatorcontrib><creatorcontrib>Deuster, Oliver</creatorcontrib><creatorcontrib>Aljabari, Bayan</creatorcontrib><creatorcontrib>Egensperger, Rupert</creatorcontrib><creatorcontrib>Neff, Frauke</creatorcontrib><creatorcontrib>Jessen, Frank</creatorcontrib><creatorcontrib>Popp, Julius</creatorcontrib><creatorcontrib>Noelker, Carmen</creatorcontrib><creatorcontrib>Reese, Jens Peter</creatorcontrib><creatorcontrib>Al-Abed, Yousef</creatorcontrib><creatorcontrib>Dodel, Richard</creatorcontrib><title>The role of macrophage migration inhibitory factor in Alzheimer's disease</title><title>Molecular medicine (Cambridge, Mass.)</title><addtitle>Mol Med</addtitle><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). 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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.</description><subject>Aged</subject><subject>Alzheimer Disease - cerebrospinal fluid</subject><subject>Alzheimer Disease - metabolism</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Brain - metabolism</subject><subject>Brain Chemistry</subject><subject>Cell Survival - drug effects</subject><subject>Female</subject><subject>Histocytochemistry</subject><subject>Humans</subject><subject>Intramolecular Oxidoreductases - antagonists & inhibitors</subject><subject>Intramolecular Oxidoreductases - cerebrospinal fluid</subject><subject>Intramolecular Oxidoreductases - metabolism</subject><subject>Isoxazoles - pharmacology</subject><subject>Macrophage Migration-Inhibitory Factors - antagonists & inhibitors</subject><subject>Macrophage Migration-Inhibitory Factors - cerebrospinal fluid</subject><subject>Macrophage Migration-Inhibitory Factors - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Neuroblastoma</subject><subject>Protease Nexins</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Statistics, Nonparametric</subject><subject>Tumor Cells, Cultured</subject><issn>1076-1551</issn><issn>1528-3658</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE9LAzEQxYMotlY_gBfJzdPWTLJJNxehFP8UCl7qOWSz2W5kd1OSVaif3tRq0dMMM7w3834IXQOZUgB51_m2s9WUEiKnhABlJ2gMnBYZE7w4TT2ZiQw4hxG6iPGNEAo85-doREnSCJBjtFw3FgffWuxr3GkT_LbRG4s7twl6cL7Hrm9c6QYfdrjWJtU0wfP2s7Gus-E24spFq6O9RGe1bqO9-qkT9Pr4sF48Z6uXp-VivspMLvIhKyUvag2MM5MeqGBWk5yQWlCqSyNYVTJOOWhtheQ0FzaHopTSgDDcFrmVbILuD77b9zKlN7Yfgm7VNrhOh53y2qn_m941auM_FC2oFCCSARwMUtgYg62PWiBqz1UduKo9V_XNNWlu_h49Kn5Bsi_EpXZY</recordid><startdate>20100301</startdate><enddate>20100301</enddate><creator>Bacher, Michael</creator><creator>Deuster, Oliver</creator><creator>Aljabari, Bayan</creator><creator>Egensperger, Rupert</creator><creator>Neff, Frauke</creator><creator>Jessen, Frank</creator><creator>Popp, Julius</creator><creator>Noelker, Carmen</creator><creator>Reese, Jens Peter</creator><creator>Al-Abed, Yousef</creator><creator>Dodel, Richard</creator><general>ScholarOne</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20100301</creationdate><title>The role of macrophage migration inhibitory factor in Alzheimer's disease</title><author>Bacher, Michael ; Deuster, Oliver ; Aljabari, Bayan ; Egensperger, Rupert ; Neff, Frauke ; Jessen, Frank ; Popp, Julius ; Noelker, Carmen ; Reese, Jens Peter ; Al-Abed, Yousef ; Dodel, Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-b958fa1353c619d17f0400f622abc63db35251aae695246e418b99c16c5e84e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Aged</topic><topic>Alzheimer Disease - cerebrospinal fluid</topic><topic>Alzheimer Disease - metabolism</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Brain - metabolism</topic><topic>Brain Chemistry</topic><topic>Cell Survival - drug effects</topic><topic>Female</topic><topic>Histocytochemistry</topic><topic>Humans</topic><topic>Intramolecular Oxidoreductases - antagonists & inhibitors</topic><topic>Intramolecular Oxidoreductases - cerebrospinal fluid</topic><topic>Intramolecular Oxidoreductases - metabolism</topic><topic>Isoxazoles - pharmacology</topic><topic>Macrophage Migration-Inhibitory Factors - antagonists & inhibitors</topic><topic>Macrophage Migration-Inhibitory Factors - cerebrospinal fluid</topic><topic>Macrophage Migration-Inhibitory Factors - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Neuroblastoma</topic><topic>Protease Nexins</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Statistics, Nonparametric</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bacher, Michael</creatorcontrib><creatorcontrib>Deuster, Oliver</creatorcontrib><creatorcontrib>Aljabari, Bayan</creatorcontrib><creatorcontrib>Egensperger, Rupert</creatorcontrib><creatorcontrib>Neff, Frauke</creatorcontrib><creatorcontrib>Jessen, Frank</creatorcontrib><creatorcontrib>Popp, Julius</creatorcontrib><creatorcontrib>Noelker, Carmen</creatorcontrib><creatorcontrib>Reese, Jens Peter</creatorcontrib><creatorcontrib>Al-Abed, Yousef</creatorcontrib><creatorcontrib>Dodel, Richard</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular medicine (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bacher, Michael</au><au>Deuster, Oliver</au><au>Aljabari, Bayan</au><au>Egensperger, Rupert</au><au>Neff, Frauke</au><au>Jessen, Frank</au><au>Popp, Julius</au><au>Noelker, Carmen</au><au>Reese, Jens Peter</au><au>Al-Abed, Yousef</au><au>Dodel, Richard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of macrophage migration inhibitory factor in Alzheimer's disease</atitle><jtitle>Molecular medicine (Cambridge, Mass.)</jtitle><addtitle>Mol Med</addtitle><date>2010-03-01</date><risdate>2010</risdate><volume>16</volume><issue>3-4</issue><spage>116</spage><epage>121</epage><pages>116-121</pages><issn>1076-1551</issn><eissn>1528-3658</eissn><abstract>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. 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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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