Development of a platelet-activating factor antagonist for HIV-1 associated neurocognitive disorders

J Neuroimmunol. 2009 Aug 18;213(1-2):47-59. doi: 10.1016/j.jneuroim.2009.06.002. Epub 2009 Jun 21.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Dementia Complex / drug therapy*
  • AIDS Dementia Complex / immunology
  • AIDS Dementia Complex / metabolism
  • 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
  • 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
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use
  • Platelet Activating Factor / antagonists & inhibitors*
  • Platelet Activating Factor / metabolism

Substances

  • Anti-Inflammatory Agents
  • Immunologic Factors
  • Inflammation Mediators
  • NF-kappa B
  • PMS 601
  • Piperazines
  • Platelet Activating Factor
  • Focal Adhesion Kinase 2
  • Ptk2b protein, mouse