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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) 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.
AuthorsDawn Eggert, Prasanta K Dash, Nawal Serradji, Chang-Zhi Dong, Pascal Clayette, Francoise Heymans, Huanyu Dou, Santhi Gorantla, Harris A Gelbard, Larisa Poluektova, Howard E Gendelman
JournalJournal of neuroimmunology (J Neuroimmunol) Vol. 213 Issue 1-2 Pg. 47-59 (Aug 18 2009) ISSN: 1872-8421 [Electronic] Netherlands
PMID19541372 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Anti-Inflammatory Agents
  • Immunologic Factors
  • Inflammation Mediators
  • NF-kappa B
  • PMS 601
  • Piperazines
  • Platelet Activating Factor
  • Focal Adhesion Kinase 2
  • Ptk2b protein, mouse
Topics
  • AIDS Dementia Complex (drug therapy, immunology, metabolism)
  • Animals
  • Anti-Inflammatory Agents (pharmacology, therapeutic use)
  • Brain (drug effects, metabolism, physiopathology)
  • Cell Death (drug effects, immunology)
  • Cells, Cultured
  • Cognition Disorders (drug therapy, immunology, metabolism)
  • Disease Models, Animal
  • Focal Adhesion Kinase 2 (drug effects, metabolism)
  • Giant Cells (drug effects, immunology, metabolism)
  • Gliosis (drug therapy, immunology, metabolism)
  • Humans
  • Immunologic Factors (pharmacology, therapeutic use)
  • Inflammation Mediators (agonists, metabolism)
  • Male
  • Mice
  • Mice, SCID
  • Microglia (drug effects, immunology, metabolism)
  • Monocytes (drug effects, immunology, metabolism)
  • NF-kappa B (drug effects, metabolism)
  • Piperazines (pharmacology, therapeutic use)
  • Platelet Activating Factor (antagonists & inhibitors, metabolism)

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