Abstract:

[Abstract] Objective To investigate the activation ofβ-sheet breaker peptide H102on ERK signal transduction pathway in brain of PAP double transgenic mice.Methods PAP double transgenic mice were randomly divided into model group and H102treatment group (n=10for each group). A group of C57BL/6J mice with the same genetic background was served as controls. H102(5.8mg/kg)5µL was infused by intranasal administration to mice in H102treatment group, and equal volume of blank solution of H102(chitosan, BSA) was given to mice in control group and model group. The ability of spatial reference memory was tested by Morris water maze after30days of treatment. Then immunohistochemistry tests and Western blot technique were used to detect the content of RAS, P-MEK and P-ERK proteins in mouse brain.Results (1) The ability of learning and memory was significantly lower in model group than that of control group. The ability of learning and memory was significantly improved in treatment group than that in model group (P<0.05). (2) The contents of RAS, P MEK and P-ERK in mouse brain were significantly lower in model group than those of control group, and these protein ex? pressions were significantly increased in treatment group than those in model group (P<0.01).Conclusion β-sheet break? er peptide H102can activate ERK signal transduction pathway in brain of PAP double transgenic mice, increase PAS, P MEK and P-ERK levels in nerve cells, and improve the ability of learning and memory in PAP mice.

Key words: Alzheimer's disease, neuronal apoptosis, ERK signal transduction pathway, β-sheet breaker