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Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Platelet-activating factor receptor activation. An initiator step in HIV-1 neuropathogenesis
S W Perry1, J A Hamilton, L W Tjoelker
1Department of Neurology (Child Neurology Division), the University of Rochester Medical Center, Rochester, New York 14642, USA.
Abstract:
Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system results in neuronal apoptosis. Activated HIV-1-infected monocytes secrete high levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and the phospholipid mediator platelet-activating factor (PAF). TNF-alpha and PAF are elevated in the central nervous system of patients with HIV-1-associated dementia. We now demonstrate that conditioned media from activated HIV-1-infected monocytes induces neuronal apoptosis, which can be prevented by co-incubation with PAF acetylhydrolase, the enzyme that catabolizes PAF in the central nervous system. Preceding apoptosis is a TNF-alpha-induced increase in neuronal ceramide levels. TNF-alpha-mediated neuronal apoptosis can also be blocked by co-incubation with PAF acetylhydrolase, or a PAF receptor antagonist. Blocking pathologic activation of PAF receptors may therefore be a pivotal step in the treatment of HIV-1-associated dementia.
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