Mediation of insulin growth factor-1 in Alzheimer's disease and the mechanism of PRNP genetic expression and the PI3K/Akt signaling pathway

The aim of the study was to examine the mediation of insulin growth factor-1 (IGF-1) in Alzheimer's disease (AD), as well as the underlying mechanism of the PRNP genetic expression and PI3K/Akt signaling pathway. The Aβ25-35-incubated rat adrenal pheochromocytoma cell (PC12) in vitro was established, constituting the AD model. Different doses (0, 20, 40 and 80 ng/ml) of IGF-1 were used in PC12 cells and the level of PRNP mRNA was tested after 24 h using the quantitative PCR method and the level of APP protein was assessed using western blot analysis. PC12 cells were divided into the control group (PC12 cells without Aβ25-35 treatment), model group (PC12 cells with Aβ25-35 treatment), IGF-1 80 ng/ml group, IGF-1 80 ng/ml+PI3K inhibitor LY294002 25 µmol/l group, and IGF-1 80 ng/ml+LY294002 50 µmol/l group, whose PRNP mRNA level and Akt, pAkt and APP protein level were tested 24 h later. As the dose of IGF-1 increases, the expression levels of PRNP mRNA and APP protein were more highly expressed. The difference between them was significant (P<0.05). In addition, regarding Akt protein, the expression levels of PRNP mRNA, APP protein and pAkt protein in the IGF-1 groups were significantly higher than those in the control and model groups. With the LY concentration increasing, the levels of expression of the three substances gradually decreased significantly (P<0.05). In conclusion, IGF-I can mediate the expression of the PRNP gene and APP protein through the PI3K/Akt signaling pathway, in a rat model.