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 Aβ(25–35)-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 Aβ(25–35) treatment), model group (PC12 cells with Aβ(25–35) 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.