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
Hauptverfasser:	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
Format:	Artikel
Sprache:	eng
Schlagworte:	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
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Zusammenfassung:	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.
ISSN:	0165-5728 1872-8421
DOI:	10.1016/j.jneuroim.2009.06.002