HIF-1α acts as an intracellular sensor for hypoxia and promotes the cells to adapt to hypoxic/ischemic conditions (Zis et al., 2015), thus we hypothesized that Nrdp1 might interact with or suppress HIF-1α to promote neuronal cell death under OGD conditions. To test this possibility, we transfected primary cortical neurons and PC12 cells with Ad-control, Ad-Nrdp1, Ad-si-control or Ad-si-Nrdp1 before exposing to OGD for 6 h. HIF-1α protein levels were analyzed by western blot. As shown in Figures 4A,B, 6-h OGD induced a significant increase in the accumulation of HIF-1α protein in both primary neurons and PC12 cells transfected with Ad-si-control, and of note, this increase was further augmented or attenuated when Nrdp1 was knocked down by Ad-si-Nrdp1 or overexpressed by Ad-Nrdp1, respectively (Figures 4C,D). These data suggest that Nrdp1 may act as a negative regulator for HIF-1α expression in neurons under OGD conditions.