Development of a platelet-activating factor antagonist for HIV-1 associated neurocognitive disorders
Abstract The neuroregulatory activities of PMS-601, a platelet activating factor antagonist, were investigated in laboratory and animal models of HIV-1 encephalitis (HIVE). For the former, PMS-601 reduced monocyte-derived macrophage pro-inflammatory secretions, multinucleated giant cell (MGC) format...
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| Veröffentlicht in: | Journal of neuroimmunology 2009-08, Vol.213 (1), p.47-59 |
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| creator | Eggert, Dawn Dash, Prasanta K Serradji, Nawal Dong, Chang-Zhi Clayette, Pascal Heymans, Francoise Dou, Huanyu Gorantla, Santhi Gelbard, Harris A Poluektova, Larisa Gendelman, Howard E |
| description | Abstract The neuroregulatory activities of PMS-601, a platelet activating factor antagonist, were investigated in laboratory and animal models of HIV-1 encephalitis (HIVE). For the former, PMS-601 reduced monocyte-derived macrophage pro-inflammatory secretions, multinucleated giant cell (MGC) formation, and neuronal loss independent of antiretroviral responses. PMS-601 treatment of HIVE severe combined immunodeficient mice showed reduced microgliosis, MGCs and neurodegeneration. These observations support the further development of PMS-601 as an adjunctive therapy for HIV-1 associated neurocognitive disorders. |
| doi_str_mv | 10.1016/j.jneuroim.2009.06.002 |
| format | Article |
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For the former, PMS-601 reduced monocyte-derived macrophage pro-inflammatory secretions, multinucleated giant cell (MGC) formation, and neuronal loss independent of antiretroviral responses. PMS-601 treatment of HIVE severe combined immunodeficient mice showed reduced microgliosis, MGCs and neurodegeneration. These observations support the further development of PMS-601 as an adjunctive therapy for HIV-1 associated neurocognitive disorders.</description><identifier>ISSN: 0165-5728</identifier><identifier>EISSN: 1872-8421</identifier><identifier>DOI: 10.1016/j.jneuroim.2009.06.002</identifier><identifier>PMID: 19541372</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>AIDS Dementia Complex - drug therapy ; AIDS Dementia Complex - immunology ; AIDS Dementia Complex - metabolism ; Allergy and Immunology ; Animals ; Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Brain - drug effects ; Brain - metabolism ; Brain - physiopathology ; Cell Death - drug effects ; Cell Death - immunology ; Cells, Cultured ; Cognition Disorders - drug therapy ; Cognition Disorders - immunology ; Cognition Disorders - metabolism ; Disease Models, Animal ; Focal Adhesion Kinase 2 - drug effects ; Focal Adhesion Kinase 2 - metabolism ; Giant Cells - drug effects ; Giant Cells - immunology ; Giant Cells - metabolism ; Gliosis - drug therapy ; Gliosis - immunology ; Gliosis - metabolism ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Humans ; Immunologic Factors - pharmacology ; Immunologic Factors - therapeutic use ; Inflammation Mediators - agonists ; Inflammation Mediators - metabolism ; Male ; Mice ; Mice, SCID ; Microglia - drug effects ; Microglia - immunology ; Microglia - metabolism ; Monocytes - drug effects ; Monocytes - immunology ; Monocytes - metabolism ; Multinucleated giant cell ; Neurology ; NF-kappa B - drug effects ; NF-kappa B - metabolism ; Nuclear factor kappa beta ; Piperazines - pharmacology ; Piperazines - therapeutic use ; Platelet activating factor ; Platelet Activating Factor - antagonists & inhibitors ; Platelet Activating Factor - metabolism ; PMS-601 ; Proline-rich tyrosine kinase 2</subject><ispartof>Journal of neuroimmunology, 2009-08, Vol.213 (1), p.47-59</ispartof><rights>Elsevier B.V.</rights><rights>2009 Elsevier B.V.</rights><rights>2009 Elsevier B.V. All rights reserved. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c555t-e65601d6200ae05c6e02788cf0f543f0f03245a081df45a9e3b7f246418b01ba3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jneuroim.2009.06.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19541372$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eggert, Dawn</creatorcontrib><creatorcontrib>Dash, Prasanta K</creatorcontrib><creatorcontrib>Serradji, Nawal</creatorcontrib><creatorcontrib>Dong, Chang-Zhi</creatorcontrib><creatorcontrib>Clayette, Pascal</creatorcontrib><creatorcontrib>Heymans, Francoise</creatorcontrib><creatorcontrib>Dou, Huanyu</creatorcontrib><creatorcontrib>Gorantla, Santhi</creatorcontrib><creatorcontrib>Gelbard, Harris A</creatorcontrib><creatorcontrib>Poluektova, Larisa</creatorcontrib><creatorcontrib>Gendelman, Howard E</creatorcontrib><title>Development of a platelet-activating factor antagonist for HIV-1 associated neurocognitive disorders</title><title>Journal of neuroimmunology</title><addtitle>J Neuroimmunol</addtitle><description>Abstract The neuroregulatory activities of PMS-601, a platelet activating factor antagonist, were investigated in laboratory and animal models of HIV-1 encephalitis (HIVE). For the former, PMS-601 reduced monocyte-derived macrophage pro-inflammatory secretions, multinucleated giant cell (MGC) formation, and neuronal loss independent of antiretroviral responses. PMS-601 treatment of HIVE severe combined immunodeficient mice showed reduced microgliosis, MGCs and neurodegeneration. These observations support the further development of PMS-601 as an adjunctive therapy for HIV-1 associated neurocognitive disorders.</description><subject>AIDS Dementia Complex - drug therapy</subject><subject>AIDS Dementia Complex - immunology</subject><subject>AIDS Dementia Complex - metabolism</subject><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Brain - physiopathology</subject><subject>Cell Death - drug effects</subject><subject>Cell Death - immunology</subject><subject>Cells, Cultured</subject><subject>Cognition Disorders - drug therapy</subject><subject>Cognition Disorders - immunology</subject><subject>Cognition Disorders - metabolism</subject><subject>Disease Models, Animal</subject><subject>Focal Adhesion Kinase 2 - drug effects</subject><subject>Focal Adhesion Kinase 2 - metabolism</subject><subject>Giant Cells - drug effects</subject><subject>Giant Cells - immunology</subject><subject>Giant Cells - metabolism</subject><subject>Gliosis - drug therapy</subject><subject>Gliosis - immunology</subject><subject>Gliosis - metabolism</subject><subject>Human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>Immunologic Factors - pharmacology</subject><subject>Immunologic Factors - therapeutic use</subject><subject>Inflammation Mediators - agonists</subject><subject>Inflammation Mediators - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Microglia - drug effects</subject><subject>Microglia - immunology</subject><subject>Microglia - metabolism</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - immunology</subject><subject>Monocytes - metabolism</subject><subject>Multinucleated giant cell</subject><subject>Neurology</subject><subject>NF-kappa B - drug effects</subject><subject>NF-kappa B - metabolism</subject><subject>Nuclear factor kappa beta</subject><subject>Piperazines - pharmacology</subject><subject>Piperazines - therapeutic use</subject><subject>Platelet activating factor</subject><subject>Platelet Activating Factor - antagonists & inhibitors</subject><subject>Platelet Activating Factor - metabolism</subject><subject>PMS-601</subject><subject>Proline-rich tyrosine kinase 2</subject><issn>0165-5728</issn><issn>1872-8421</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkstu1DAUhi0EotOBV6iyYpf0HCd2kk0FaoFWqsSCy9byOCeDQ2IPdjJS3x4PM1w33fjY8v-fiz8zdoFQIKC8HIrB0RK8nQoO0BYgCwD-hK2wqXneVByfslUSilzUvDlj5zEOACjKqn3OzrAVFZY1X7HuhvY0-t1Ebs58n-lsN-qZRppzbWa717N126xPex8y7Wa99c7GOevT8fbuS46ZjtEbmzxd9rMj47fOJidlnY0-dBTiC_as12Okl6e4Zp_fvf10fZvff3h_d_3mPjdCiDknKSRgJ9NAmkAYScDrpjE99KIq0wolr4SGBrs-xZbKTd3zSlbYbAA3ulyzq2Pe3bKZqDNppqBHtQt20uFBeW3VvzfOflVbv1e8FjWmGmv26pQg-O8LxVlNNhoaR-3IL1HJpGsFPi7kgAlBLZJQHoUm-BgD9b-7QVAHkmpQv0iqA0kFUiWSyXjx9yx_bCd0SfD6KKD0ontLQUVjyRnqbCAzq87bx2tc_ZfCjNZZo8dv9EBx8EtwiZdCFbkC9fHwnw7fCdrkRonlD7D2yhQ</recordid><startdate>20090818</startdate><enddate>20090818</enddate><creator>Eggert, Dawn</creator><creator>Dash, Prasanta K</creator><creator>Serradji, Nawal</creator><creator>Dong, Chang-Zhi</creator><creator>Clayette, Pascal</creator><creator>Heymans, Francoise</creator><creator>Dou, Huanyu</creator><creator>Gorantla, Santhi</creator><creator>Gelbard, Harris A</creator><creator>Poluektova, Larisa</creator><creator>Gendelman, Howard E</creator><general>Elsevier B.V</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>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090818</creationdate><title>Development of a platelet-activating factor antagonist for HIV-1 associated neurocognitive disorders</title><author>Eggert, Dawn ; Dash, Prasanta K ; Serradji, Nawal ; Dong, Chang-Zhi ; Clayette, Pascal ; Heymans, Francoise ; Dou, Huanyu ; Gorantla, Santhi ; Gelbard, Harris A ; Poluektova, Larisa ; Gendelman, Howard E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c555t-e65601d6200ae05c6e02788cf0f543f0f03245a081df45a9e3b7f246418b01ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>AIDS Dementia Complex - drug therapy</topic><topic>AIDS Dementia Complex - immunology</topic><topic>AIDS Dementia Complex - metabolism</topic><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Brain - physiopathology</topic><topic>Cell Death - drug effects</topic><topic>Cell Death - immunology</topic><topic>Cells, Cultured</topic><topic>Cognition Disorders - drug therapy</topic><topic>Cognition Disorders - immunology</topic><topic>Cognition Disorders - metabolism</topic><topic>Disease Models, Animal</topic><topic>Focal Adhesion Kinase 2 - drug effects</topic><topic>Focal Adhesion Kinase 2 - metabolism</topic><topic>Giant Cells - drug effects</topic><topic>Giant Cells - immunology</topic><topic>Giant Cells - metabolism</topic><topic>Gliosis - drug therapy</topic><topic>Gliosis - immunology</topic><topic>Gliosis - metabolism</topic><topic>Human immunodeficiency virus</topic><topic>Human immunodeficiency virus 1</topic><topic>Humans</topic><topic>Immunologic Factors - pharmacology</topic><topic>Immunologic Factors - therapeutic use</topic><topic>Inflammation Mediators - agonists</topic><topic>Inflammation Mediators - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Microglia - drug effects</topic><topic>Microglia - immunology</topic><topic>Microglia - metabolism</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - immunology</topic><topic>Monocytes - metabolism</topic><topic>Multinucleated giant cell</topic><topic>Neurology</topic><topic>NF-kappa B - drug effects</topic><topic>NF-kappa B - metabolism</topic><topic>Nuclear factor kappa beta</topic><topic>Piperazines - pharmacology</topic><topic>Piperazines - therapeutic use</topic><topic>Platelet activating factor</topic><topic>Platelet Activating Factor - antagonists & inhibitors</topic><topic>Platelet Activating Factor - metabolism</topic><topic>PMS-601</topic><topic>Proline-rich tyrosine kinase 2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eggert, Dawn</creatorcontrib><creatorcontrib>Dash, Prasanta K</creatorcontrib><creatorcontrib>Serradji, Nawal</creatorcontrib><creatorcontrib>Dong, Chang-Zhi</creatorcontrib><creatorcontrib>Clayette, Pascal</creatorcontrib><creatorcontrib>Heymans, Francoise</creatorcontrib><creatorcontrib>Dou, Huanyu</creatorcontrib><creatorcontrib>Gorantla, Santhi</creatorcontrib><creatorcontrib>Gelbard, Harris A</creatorcontrib><creatorcontrib>Poluektova, Larisa</creatorcontrib><creatorcontrib>Gendelman, Howard E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neuroimmunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eggert, Dawn</au><au>Dash, Prasanta K</au><au>Serradji, Nawal</au><au>Dong, Chang-Zhi</au><au>Clayette, Pascal</au><au>Heymans, Francoise</au><au>Dou, Huanyu</au><au>Gorantla, Santhi</au><au>Gelbard, Harris A</au><au>Poluektova, Larisa</au><au>Gendelman, Howard E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a platelet-activating factor antagonist for HIV-1 associated neurocognitive disorders</atitle><jtitle>Journal of neuroimmunology</jtitle><addtitle>J Neuroimmunol</addtitle><date>2009-08-18</date><risdate>2009</risdate><volume>213</volume><issue>1</issue><spage>47</spage><epage>59</epage><pages>47-59</pages><issn>0165-5728</issn><eissn>1872-8421</eissn><abstract>Abstract The neuroregulatory activities of PMS-601, a platelet activating factor antagonist, were investigated in laboratory and animal models of HIV-1 encephalitis (HIVE). For the former, PMS-601 reduced monocyte-derived macrophage pro-inflammatory secretions, multinucleated giant cell (MGC) formation, and neuronal loss independent of antiretroviral responses. PMS-601 treatment of HIVE severe combined immunodeficient mice showed reduced microgliosis, MGCs and neurodegeneration. These observations support the further development of PMS-601 as an adjunctive therapy for HIV-1 associated neurocognitive disorders.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>19541372</pmid><doi>10.1016/j.jneuroim.2009.06.002</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | AIDS Dementia Complex - drug therapy AIDS Dementia Complex - immunology AIDS Dementia Complex - metabolism Allergy and Immunology Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Brain - drug effects Brain - metabolism Brain - physiopathology Cell Death - drug effects Cell Death - immunology Cells, Cultured Cognition Disorders - drug therapy Cognition Disorders - immunology Cognition Disorders - metabolism Disease Models, Animal Focal Adhesion Kinase 2 - drug effects Focal Adhesion Kinase 2 - metabolism Giant Cells - drug effects Giant Cells - immunology Giant Cells - metabolism Gliosis - drug therapy Gliosis - immunology Gliosis - metabolism Human immunodeficiency virus Human immunodeficiency virus 1 Humans Immunologic Factors - pharmacology Immunologic Factors - therapeutic use Inflammation Mediators - agonists Inflammation Mediators - metabolism Male Mice Mice, SCID Microglia - drug effects Microglia - immunology Microglia - metabolism Monocytes - drug effects Monocytes - immunology Monocytes - metabolism Multinucleated giant cell Neurology NF-kappa B - drug effects NF-kappa B - metabolism Nuclear factor kappa beta Piperazines - pharmacology Piperazines - therapeutic use Platelet activating factor Platelet Activating Factor - antagonists & inhibitors Platelet Activating Factor - metabolism PMS-601 Proline-rich tyrosine kinase 2 |
| title | Development of a platelet-activating factor antagonist for HIV-1 associated neurocognitive disorders |
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