[Effect of βsheet blocking peptide H102 on APP metabolic enzymes in hippocampal brain of double transgenic AD mice].

OBJECTIVE:To investigate the effect of β-sheet breaker peptide H102 on APP associated secretase in the hippocampus brain regions of APP/PS1 double transgenic mice(AD mice). METHODS:Thirty 6-month-old APP/PS1 double transgenic mice were randomly divided into AD group and H102 group, a group of C57BL/6J mice with the same age, number and background was set as controls(n=15). H102 (5.8 mg/kg) 5 μl was infused by intranasal administration to mice in H102 treatment group, and equal volume of blank solution of H102 was given to mice in control group and AD group. The ability of spatial reference memory was tested by Morris water maze after 30 days of treatment. And then immunohistochemistry tests and Western blot were used to detect the content of α-secretase (ADAM10, ADAM17), β-secretase (BACE1), γ-secretase (PS1, APH1a, PEN2) in the hippocampus brain regions. RESULTS:Compared with the control group, the expression of BACE1, PS1, PEN-2 and APH1-a protein in the hippocampus of AD group were significantly increased, ADAM10, ADAM17 protein expression were significantly reduced (P<0.05); Compared with the model group, H102 could significantly improve the spatial learning and memory ability of AD mice, significantly decreased the expression of BACE1, PS1, PEN-2 and APH1-a protein in the hippocampus, significantly increased the expression of ADAM10 and ADAM17 protein(P<0.05). CONCLUSIONS:β sheet peptides blocked H102 can reduce the formation of Aβ in the hippocampus brain area, improve the activity of α-secretase in the hippocampus brain region, decrease the activity of β-and γ-secretase, improve the learning and memory ability of AD mice.

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