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- W2005478511 abstract "Although a recent study opens perspectives for therapy of AD by gamma-secretase inhibition (Dewachter et al. J Neurosci. 2002;22:3445–53), but it has not been reported for herbal therapy in inhibiting gamma-secretase substrate (PS1) related to production of Abeta production. This study aimed to investigate effects of GETO, a combination of herbal active components, on Abeta production and beta-secretase substrate (BACE1) and gamma-secretase substrate (PS1). Thirty APPV717I transgenic mice aged 3 months were randomly divided into a APP group which was given distilled water, a APP+donepezil group which was administered donepezil (0.92mg/kg/d), and three APP+GETO groups which were separately administered with a small dose (0.075g/kg/d), a middle dose (0.15g/kg/d), a large (0.3g/kg/d) per day for 8 months. Six vehicle mice of C57BL/6J were given distilled water. Immunohistochemistry and Western blot analysis were used in the determining Abeta, BACE1 and PS1 in the hippocampus of mice. Compared to APP or APP+donepezil group, expression of total Abeta level in the large dose of GETO was significantly decreased, which closes to the level in C57BL/6J mice. Western blot by antibodies against Abeta protein showed that the large dose had normalized Abeta band density. There was significantly increased expression of PS1 in the large dose, which also closes to those in C57BL /6J mice and lower than APP or APP+donepezil group. Although expression of BACE1 in the large dose was lower than those in APP group but much higher than those in C57BL/6J mice. The decreased BACE1 level in APP+donepezil was still greater than those in C57BL/6J mice. The decreased BACE1 level in APP+donepezil was also greater than those in C57BL/6J mice. This data suggests that GETO reduces Abeta production in the brain of APPV717I mice perhaps by inhibiting PS1 activity rather than BACE1. The large dose of GETO has better benefit in the inhibition of PS1 than middle or small dose. This study promises a potential strategy for preventing the development of AD. This work was supported by The 973 Project (Grant No. 2003CB517104), The 111 Project (Grant No. B08006), The NSFC Project (Grant No. 30672693), and Chutian Scholars Project." @default.
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- W2005478511 date "2008-07-01" @default.
- W2005478511 modified "2023-09-25" @default.
- W2005478511 title "P2-368: GETO reduces Aβ production by gamma-secretase inhibition" @default.
- W2005478511 doi "https://doi.org/10.1016/j.jalz.2008.05.1446" @default.
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