Neuroprotective effects of LMW and HMW FGF2 against amyloid beta toxicity in primary cultured hippocampal neurons

•LMW FGF2 and HMW FGF2 protected against Aβ1-42- induced neurotoxicity in the neurons.•HMW FGF2 had stronger neuroprotective effect.•The AKT signaling pathway mediates the neuroprotective effect of FGF2.•Differential effects of different forms of FGF2 should be considered in future studies. Basic Fibroblast growth factor (FGF2) is important in development and maintenance of central nervous system function. Studies have demonstrated that low molecular weight (LMW) FGF2 is a neuroprotective factor against various insults in vivo and in vitro. In the present study we investigated the neuroprotective effects of high molecular weight (HMW) and LMW FGF2 against amyloid beta-induced neurotoxicity. The results showed that both LMW and HMW FGF2 attenuated the amyloid beta toxicity in the primary cultured hippocampal neurons as measured by WST and LDH release assay. Moreover, the analysis suggested that HMW FGF2 had stronger neuroprotective effect than LMW FGF2. We then demonstrated that LMW and HMW FGF2 activated the ERK and AKT signaling pathways in a similar way. Furthermore, using the ERK inhibitor and AKT inhibitor, we found that the AKT signaling but not ERK signaling pathway was required for the neuroprotective effects of FGF2. Taken together, these results showed the neuroprotective effects of different forms of FGF2 in an AD model and the mechanism underlying the neuroprotection.