Development of a platelet-activating factor antagonist for HIV-1 associated neurocognitive disorders.
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.
Eggert
Dawn
D
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Dash
Prasanta K
PK
Serradji
Nawal
N
Dong
Chang-Zhi
CZ
Clayette
Pascal
P
Heymans
Francoise
F
Dou
Huanyu
H
Gorantla
Santhi
S
Gelbard
Harris A
HA
Poluektova
Larisa
L
Gendelman
Howard E
HE
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D051418:Focal Adhesion Kinase 2 / Q000187:drug effects / Q000378:metabolism; D015726:Giant Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000819:agonists / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D018836:Inflammation Mediators; D016328:NF-kappa B; C410215:PMS 601; D010879:Piperazines; D010972:Platelet Activating Factor; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse