Neurotoxic Effects of HIV-1 gp120 and Interaction with Allopregnanolone

With increasing incidence of HIV and its associated neurocognitive disorders, there has emerged a need for an antiviral with improved delivery to the CNS. In searching for drug candidates that meet these criteria, some have noted that certain steroid hormones like estrogen and progesterone that naturally accumulate in the CNS show neuroprotective effects in cells exposed to HIV proteins. This investigation focused on testing the potential protective effects of the progesterone metabolite, allopregnanolone (AlloP), against HIV protein gp120-mediated neurotoxicity. Experiments were conducted using SH-SY5Y neuroblastoma cells that were exposed to varying concentrations of AlloP (0-100 nM) in conjunction with one of three gp120 conditions (vehicle, X4 gp120 at 500pM, R5 gp120 at 500 pM). Once treated, plates were imaged at 24-hour intervals for 48 hours and assessed for proportion of cell death. Analysis of the results found that AlloP had no significant influence over cell death and that gp120 only induced a significant amount of cell death once deglycosylated. Further investigation will be needed to assess the influence of AlloP and natural steroid products on the direct and indirect glial-mediated neurotoxic mechanisms of HIV-1 gp120