Mounting evidence suggests that HIF-1α is an essential transcriptional regulator of various vital processes in neurons including the adaptation of cells to hypoxic environments (Barteczek et al., 2017), cell proliferation (Zhang et al., 2017), cell apoptosis (Yin J. et al., 2017) and metabolism (Carmeliet et al., 1998; Cho et al., 2015). In the brain, HIF-1α has been reported to act as a pivotal protective regulator in ischemic brain injury (Fan et al., 2009; Singh et al., 2012; Zhang et al., 2014). Baranova et al. (2007) found that knockdown of neuronal HIF-1α enhances ischemic brain injury. Activation of HIF-1α-associated signaling cascades, such as EPO pathway (Liu et al., 2006; Ryou et al., 2012) and VEGF pathway (Yin W. et al., 2017) in neurons could protect the brain from I/R damage through increasing microvascular density and/or restoring local blood flow and oxygen supply. Yang X. S. et al. (2017) found that HIF-1α involved in necroptosis contributed to ischemic brain injury induced by OGD and MCAO. Inhibition of the 20S proteasomal activity can protects HIF-1α from degradation and provides neuroprotection in cerebral ischemia (Badawi and Shi, 2017). Here we show that 6-h OGD without re-oxygenation induces HIF-1α protein accumulation in neuronal cells, and this change is enhanced or suppressed by overexpression or knockdown of Nrdp1, respectively. This important observation has evoked us to further explore the interaction between Nrdp1 and HIF-1α in OGD-treated neurons.