HIV-1 Tat neurotoxicity: a model of acute and chronic exposure, and neuroprotection by gene delivery of antioxidant enzymes.

摘要: HIV-associated neurocognitive disorder (HAND) is an increasingly common, progressive disease characterized by neuronal loss and progressively deteriorating CNS function. HIV-1 gene products, particularly gp120 Tat elicit reactive oxygen species (ROS) that lead to oxidant injury cause neuron apoptosis. Understanding of, developing therapies for, HAND requires accessible models of the disease. We have devised experimental approaches studying acute chronic effects on CNS. studied exposure injecting recombinant protein into caudate-putamen (CP). Ongoing expression, which more closely mimics infection brain, was delivering Tat-expression over time using SV40-derived delivery vector, SV(Tat). Both induced lipid peroxidation Finally, prior administration SV40 vectors carrying antioxidant enzymes, copper/zinc superoxide dismutase (SOD1) or glutathione peroxidase (GPx1), protected from Tat-induced apoptosis oxidative injury. Thus, injection expression SV(Tat), rat CP respectively ongoing stress in neurons may represent useful animal for pathogenesis and, potentially, treatment Tat-related damage.