Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer’s disease-related pathology
Alzheimer’s disease (AD) is the most common cause of dementia worldwide. The pathogenesis of this neurodegenerative disease, currently without curative treatment, is associated with the accumulation of amyloid β (Aβ) in brain parenchyma and cerebral vasculature. AD patients are unable to clear this...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2013-01, Vol.110 (5), p.1941-1946 |
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| creator | Michaud, Jean-Philippe Hallé, Maxime Lampron, Antoine Thériault, Peter Préfontaine, Paul Filali, Mohammed Tribout-Jover, Pascale Lanteigne, Anne-Marie Jodoin, Rachel Cluff, Christopher Brichard, Vincent Palmantier, Rémi Pilorget, Anthony Larocque, Daniel Rivest, Serge |
| description | Alzheimer’s disease (AD) is the most common cause of dementia worldwide. The pathogenesis of this neurodegenerative disease, currently without curative treatment, is associated with the accumulation of amyloid β (Aβ) in brain parenchyma and cerebral vasculature. AD patients are unable to clear this toxic peptide, leading to Aβ accumulation in their brains and, presumably, the pathology associated with this devastating disease. Compounds that stimulate the immune system to clear Aβ may therefore have great therapeutic potential in AD patients. Monophosphoryl lipid A (MPL) is an LPS-derived Toll-like receptor 4 agonist that exhibits unique immunomodulatory properties at doses that are nonpyrogenic. We show here that repeated systemic injections of MPL, but not LPS, significantly improved AD-related pathology in APP ₛwₑ/PS1 mice. MPL treatment led to a significant reduction in Aβ load in the brain of these mice, as well as enhanced cognitive function. MPL induced a potent phagocytic response by microglia while triggering a moderate inflammatory reaction. Our data suggest that the Toll-like receptor 4 agonist MPL may be a treatment for AD. |
| doi_str_mv | 10.1073/pnas.1215165110 |
| format | Article |
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The pathogenesis of this neurodegenerative disease, currently without curative treatment, is associated with the accumulation of amyloid β (Aβ) in brain parenchyma and cerebral vasculature. AD patients are unable to clear this toxic peptide, leading to Aβ accumulation in their brains and, presumably, the pathology associated with this devastating disease. Compounds that stimulate the immune system to clear Aβ may therefore have great therapeutic potential in AD patients. Monophosphoryl lipid A (MPL) is an LPS-derived Toll-like receptor 4 agonist that exhibits unique immunomodulatory properties at doses that are nonpyrogenic. We show here that repeated systemic injections of MPL, but not LPS, significantly improved AD-related pathology in APP ₛwₑ/PS1 mice. MPL treatment led to a significant reduction in Aβ load in the brain of these mice, as well as enhanced cognitive function. MPL induced a potent phagocytic response by microglia while triggering a moderate inflammatory reaction. Our data suggest that the Toll-like receptor 4 agonist MPL may be a treatment for AD.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1215165110</identifier><identifier>PMID: 23322736</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences</publisher><subject>agonists ; Alzheimer disease ; Alzheimer Disease - metabolism ; Alzheimer Disease - pathology ; Alzheimer Disease - prevention & control ; Alzheimer's disease ; Alzheimers disease ; amyloid ; Amyloid beta-Protein Precursor - genetics ; Amyloid beta-Protein Precursor - metabolism ; Amyloids ; Animals ; Biological and medical sciences ; Biological Sciences ; Blotting, Western ; brain ; Brain - drug effects ; Brain - metabolism ; Brain - pathology ; Cell Line ; cognition ; Cytokines ; Cytokines - genetics ; Cytokines - metabolism ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Fundamental and applied biological sciences. Psychology ; Gene Expression - drug effects ; HEK293 Cells ; Humans ; immune system ; Immunity, Innate - drug effects ; immunomodulators ; Ligands ; lipid A ; Lipid A - administration & dosage ; Lipid A - analogs & derivatives ; Lipid A - therapeutic use ; Lipids ; Lipopolysaccharides - pharmacology ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microglia ; Microglia - cytology ; Microglia - drug effects ; Microglia - metabolism ; Microscopy, Fluorescence ; Monocytes ; neurodegenerative diseases ; neuroglia ; Neurology ; parenchyma (animal tissue) ; Pathogenesis ; Pathology ; patients ; Peptides ; Phagocytosis ; Phagocytosis - drug effects ; Presenilin-1 - genetics ; Presenilin-1 - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; Toll-like receptor 4 ; Toll-Like Receptor 4 - agonists ; Toll-Like Receptor 4 - metabolism ; toxicity ; Vaccination ; Vertebrates: nervous system and sense organs</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2013-01, Vol.110 (5), p.1941-1946</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>2014 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Jan 29, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c578t-5d64f98efdc7841f2a25b117db16459a3efea7993830366f83f215d1fd49fd2d3</citedby><cites>FETCH-LOGICAL-c578t-5d64f98efdc7841f2a25b117db16459a3efea7993830366f83f215d1fd49fd2d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/5.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41992144$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41992144$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27204581$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23322736$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Michaud, Jean-Philippe</creatorcontrib><creatorcontrib>Hallé, Maxime</creatorcontrib><creatorcontrib>Lampron, Antoine</creatorcontrib><creatorcontrib>Thériault, Peter</creatorcontrib><creatorcontrib>Préfontaine, Paul</creatorcontrib><creatorcontrib>Filali, Mohammed</creatorcontrib><creatorcontrib>Tribout-Jover, Pascale</creatorcontrib><creatorcontrib>Lanteigne, Anne-Marie</creatorcontrib><creatorcontrib>Jodoin, Rachel</creatorcontrib><creatorcontrib>Cluff, Christopher</creatorcontrib><creatorcontrib>Brichard, Vincent</creatorcontrib><creatorcontrib>Palmantier, Rémi</creatorcontrib><creatorcontrib>Pilorget, Anthony</creatorcontrib><creatorcontrib>Larocque, Daniel</creatorcontrib><creatorcontrib>Rivest, Serge</creatorcontrib><title>Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer’s disease-related pathology</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Alzheimer’s disease (AD) is the most common cause of dementia worldwide. The pathogenesis of this neurodegenerative disease, currently without curative treatment, is associated with the accumulation of amyloid β (Aβ) in brain parenchyma and cerebral vasculature. AD patients are unable to clear this toxic peptide, leading to Aβ accumulation in their brains and, presumably, the pathology associated with this devastating disease. Compounds that stimulate the immune system to clear Aβ may therefore have great therapeutic potential in AD patients. Monophosphoryl lipid A (MPL) is an LPS-derived Toll-like receptor 4 agonist that exhibits unique immunomodulatory properties at doses that are nonpyrogenic. We show here that repeated systemic injections of MPL, but not LPS, significantly improved AD-related pathology in APP ₛwₑ/PS1 mice. MPL treatment led to a significant reduction in Aβ load in the brain of these mice, as well as enhanced cognitive function. MPL induced a potent phagocytic response by microglia while triggering a moderate inflammatory reaction. Our data suggest that the Toll-like receptor 4 agonist MPL may be a treatment for AD.</description><subject>agonists</subject><subject>Alzheimer disease</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer Disease - prevention & control</subject><subject>Alzheimer's disease</subject><subject>Alzheimers disease</subject><subject>amyloid</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloids</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biological Sciences</subject><subject>Blotting, Western</subject><subject>brain</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Cell Line</subject><subject>cognition</subject><subject>Cytokines</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression - drug effects</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>immune system</subject><subject>Immunity, Innate - drug effects</subject><subject>immunomodulators</subject><subject>Ligands</subject><subject>lipid A</subject><subject>Lipid A - administration & dosage</subject><subject>Lipid A - analogs & derivatives</subject><subject>Lipid A - therapeutic use</subject><subject>Lipids</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Microglia</subject><subject>Microglia - cytology</subject><subject>Microglia - drug effects</subject><subject>Microglia - metabolism</subject><subject>Microscopy, Fluorescence</subject><subject>Monocytes</subject><subject>neurodegenerative diseases</subject><subject>neuroglia</subject><subject>Neurology</subject><subject>parenchyma (animal tissue)</subject><subject>Pathogenesis</subject><subject>Pathology</subject><subject>patients</subject><subject>Peptides</subject><subject>Phagocytosis</subject><subject>Phagocytosis - drug effects</subject><subject>Presenilin-1 - genetics</subject><subject>Presenilin-1 - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Toll-like receptor 4</subject><subject>Toll-Like Receptor 4 - agonists</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>toxicity</subject><subject>Vaccination</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkk9vFCEYxidGY9fq2ZNKYpp4mZYXmBm4NNk0_kuaeLA9E3aAHVZmGGG2up5M_BR-vX4S2ey6rR4ICe-P53lfHoriOeBTwA09GweVToFABXUFgB8UM8ACypoJ_LCYYUyakjPCjoonKa0wxqLi-HFxRCglpKH1rPh1FbwvvftiUDStGacQEUNpcv3aq8mFAX1zU4emziBtpvDdWWc08m6pBo36MISxCymvuPH5dHQazZHrxxhuTEJz_6Mzrjfx9ufvhLRLRiVTRpOVs8iopi74sNw8LR5Z5ZN5tt-Pi-t3b68uPpSXn95_vJhflm3V8KmsdM2s4MbqtuEMLFGkWgA0egE1q4SixhrVCEE5xbSuLac2P4wGq5mwmmh6XJzvdMf1oje6NcMUlZdjdL2KGxmUk_9WBtfJZbiRtKpJ00AWeLMXiOHr2qRJ9i61xns1mLBOEjimuSFOSEZf_4euwjoOeTwJhFOWGxRb6mxHtTGkFI09NANYbgOW24DlXcD5xsv7Mxz4v4lm4GQPqNQqb6MaWpfuuIZgVnG4J7R1ONhm30qCYFvgxQ5YpfwpDgQDIQgwluuvdnWrglTLmE2uPxMMNcbAgBBM_wB4hc9B</recordid><startdate>20130129</startdate><enddate>20130129</enddate><creator>Michaud, Jean-Philippe</creator><creator>Hallé, Maxime</creator><creator>Lampron, Antoine</creator><creator>Thériault, Peter</creator><creator>Préfontaine, Paul</creator><creator>Filali, Mohammed</creator><creator>Tribout-Jover, Pascale</creator><creator>Lanteigne, Anne-Marie</creator><creator>Jodoin, Rachel</creator><creator>Cluff, Christopher</creator><creator>Brichard, Vincent</creator><creator>Palmantier, Rémi</creator><creator>Pilorget, Anthony</creator><creator>Larocque, Daniel</creator><creator>Rivest, Serge</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>IQODW</scope><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20130129</creationdate><title>Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer’s disease-related pathology</title><author>Michaud, Jean-Philippe ; Hallé, Maxime ; Lampron, Antoine ; Thériault, Peter ; Préfontaine, Paul ; Filali, Mohammed ; Tribout-Jover, Pascale ; Lanteigne, Anne-Marie ; Jodoin, Rachel ; Cluff, Christopher ; Brichard, Vincent ; Palmantier, Rémi ; Pilorget, Anthony ; Larocque, Daniel ; Rivest, Serge</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c578t-5d64f98efdc7841f2a25b117db16459a3efea7993830366f83f215d1fd49fd2d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>agonists</topic><topic>Alzheimer disease</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer Disease - prevention & control</topic><topic>Alzheimer's disease</topic><topic>Alzheimers disease</topic><topic>amyloid</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Amyloids</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biological Sciences</topic><topic>Blotting, Western</topic><topic>brain</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Cell Line</topic><topic>cognition</topic><topic>Cytokines</topic><topic>Cytokines - genetics</topic><topic>Cytokines - metabolism</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression - drug effects</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>immune system</topic><topic>Immunity, Innate - drug effects</topic><topic>immunomodulators</topic><topic>Ligands</topic><topic>lipid A</topic><topic>Lipid A - administration & dosage</topic><topic>Lipid A - analogs & derivatives</topic><topic>Lipid A - therapeutic use</topic><topic>Lipids</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Microglia</topic><topic>Microglia - cytology</topic><topic>Microglia - drug effects</topic><topic>Microglia - metabolism</topic><topic>Microscopy, Fluorescence</topic><topic>Monocytes</topic><topic>neurodegenerative diseases</topic><topic>neuroglia</topic><topic>Neurology</topic><topic>parenchyma (animal tissue)</topic><topic>Pathogenesis</topic><topic>Pathology</topic><topic>patients</topic><topic>Peptides</topic><topic>Phagocytosis</topic><topic>Phagocytosis - drug effects</topic><topic>Presenilin-1 - genetics</topic><topic>Presenilin-1 - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Rodents</topic><topic>Toll-like receptor 4</topic><topic>Toll-Like Receptor 4 - agonists</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>toxicity</topic><topic>Vaccination</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Michaud, Jean-Philippe</creatorcontrib><creatorcontrib>Hallé, Maxime</creatorcontrib><creatorcontrib>Lampron, Antoine</creatorcontrib><creatorcontrib>Thériault, Peter</creatorcontrib><creatorcontrib>Préfontaine, Paul</creatorcontrib><creatorcontrib>Filali, Mohammed</creatorcontrib><creatorcontrib>Tribout-Jover, Pascale</creatorcontrib><creatorcontrib>Lanteigne, Anne-Marie</creatorcontrib><creatorcontrib>Jodoin, Rachel</creatorcontrib><creatorcontrib>Cluff, Christopher</creatorcontrib><creatorcontrib>Brichard, Vincent</creatorcontrib><creatorcontrib>Palmantier, Rémi</creatorcontrib><creatorcontrib>Pilorget, Anthony</creatorcontrib><creatorcontrib>Larocque, Daniel</creatorcontrib><creatorcontrib>Rivest, Serge</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Michaud, Jean-Philippe</au><au>Hallé, Maxime</au><au>Lampron, Antoine</au><au>Thériault, Peter</au><au>Préfontaine, Paul</au><au>Filali, Mohammed</au><au>Tribout-Jover, Pascale</au><au>Lanteigne, Anne-Marie</au><au>Jodoin, Rachel</au><au>Cluff, Christopher</au><au>Brichard, Vincent</au><au>Palmantier, Rémi</au><au>Pilorget, Anthony</au><au>Larocque, Daniel</au><au>Rivest, Serge</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer’s disease-related pathology</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2013-01-29</date><risdate>2013</risdate><volume>110</volume><issue>5</issue><spage>1941</spage><epage>1946</epage><pages>1941-1946</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Alzheimer’s disease (AD) is the most common cause of dementia worldwide. The pathogenesis of this neurodegenerative disease, currently without curative treatment, is associated with the accumulation of amyloid β (Aβ) in brain parenchyma and cerebral vasculature. AD patients are unable to clear this toxic peptide, leading to Aβ accumulation in their brains and, presumably, the pathology associated with this devastating disease. Compounds that stimulate the immune system to clear Aβ may therefore have great therapeutic potential in AD patients. Monophosphoryl lipid A (MPL) is an LPS-derived Toll-like receptor 4 agonist that exhibits unique immunomodulatory properties at doses that are nonpyrogenic. We show here that repeated systemic injections of MPL, but not LPS, significantly improved AD-related pathology in APP ₛwₑ/PS1 mice. MPL treatment led to a significant reduction in Aβ load in the brain of these mice, as well as enhanced cognitive function. MPL induced a potent phagocytic response by microglia while triggering a moderate inflammatory reaction. Our data suggest that the Toll-like receptor 4 agonist MPL may be a treatment for AD.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences</pub><pmid>23322736</pmid><doi>10.1073/pnas.1215165110</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2013-01, Vol.110 (5), p.1941-1946 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_fao_agris_US201600141220 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | agonists Alzheimer disease Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer Disease - prevention & control Alzheimer's disease Alzheimers disease amyloid Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - metabolism Amyloids Animals Biological and medical sciences Biological Sciences Blotting, Western brain Brain - drug effects Brain - metabolism Brain - pathology Cell Line cognition Cytokines Cytokines - genetics Cytokines - metabolism Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Fundamental and applied biological sciences. Psychology Gene Expression - drug effects HEK293 Cells Humans immune system Immunity, Innate - drug effects immunomodulators Ligands lipid A Lipid A - administration & dosage Lipid A - analogs & derivatives Lipid A - therapeutic use Lipids Lipopolysaccharides - pharmacology Medical sciences Mice Mice, Inbred C57BL Mice, Transgenic Microglia Microglia - cytology Microglia - drug effects Microglia - metabolism Microscopy, Fluorescence Monocytes neurodegenerative diseases neuroglia Neurology parenchyma (animal tissue) Pathogenesis Pathology patients Peptides Phagocytosis Phagocytosis - drug effects Presenilin-1 - genetics Presenilin-1 - metabolism Reverse Transcriptase Polymerase Chain Reaction Rodents Toll-like receptor 4 Toll-Like Receptor 4 - agonists Toll-Like Receptor 4 - metabolism toxicity Vaccination Vertebrates: nervous system and sense organs |
| title | Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer’s disease-related pathology |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T13%3A19%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_fao_a&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Toll-like%20receptor%204%20stimulation%20with%20the%20detoxified%20ligand%20monophosphoryl%20lipid%20A%20improves%20Alzheimer%E2%80%99s%20disease-related%20pathology&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Michaud,%20Jean-Philippe&rft.date=2013-01-29&rft.volume=110&rft.issue=5&rft.spage=1941&rft.epage=1946&rft.pages=1941-1946&rft.issn=0027-8424&rft.eissn=1091-6490&rft.coden=PNASA6&rft_id=info:doi/10.1073/pnas.1215165110&rft_dat=%3Cjstor_fao_a%3E41992144%3C/jstor_fao_a%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1283436692&rft_id=info:pmid/23322736&rft_jstor_id=41992144&rfr_iscdi=true |