Phosphofructokinase-1 Inhibition Promotes Neuronal Differentiation of Neural Stem Cells and Functional Recovery After Stroke.

Ischemic stroke is a major cause of long-term disability. Neuronal differentiation of neural stem cells (NSCs) is crucial for brain repair after stroke. However, the underlying mechanisms remain unclear. Here, the role and potential mechanisms of phosphofructokinase-1 (PFK-1), the rate-limiting enzyme of glycolysis, was investigated in stroke using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation models. We found that stroke increased the PFK-1 expression of NSCs. However, PFK-1 inhibition promoted neuronal differentiation of NSCs and facilitated the dendritic maturation of newborn neurons in vitro and in vivo. Moreover, PFK-1 inhibition also improved the spatial memory performance of MCAO rats. Additionally, we proved that the effect of PFK-1 inhibition above might be achieved by promoting β-catenin nuclear translocation and activating its downstream signaling, independent of Wnt signaling. Thus, these observations reveal a critical role of PFK-1 in stroke, which may provide a novel target for regenerative repair after stroke.