The disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between production and clearance of A beta. A major therapeutic strategy for

AD should be to decrease deposition of A beta by Selleck GW786034 the inhibition of its production and the facilitation of its degradation. Hence, the primary aim of this study was to investigate effects of GEPT, a combination of herbal extracts, on A beta levels, beta- and gamma-secretases substrate (BACE1 and PS1, respectively) associated with production of A beta and insulin-degrading enzyme (IDE) and neprilysin (NEP) related to degradation of A beta in the brain. Methods: Three-month-old-male APPV717I mice were randomly divided into five groups {Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleckchem Anti-infection Compound Library|Selleckchem Antiinfection Compound Library|Selleckchem Anti-infection Compound Library|Selleckchem Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|buy Anti-infection Compound Library|Anti-infection Compound Library ic50|Anti-infection Compound Library price|Anti-infection Compound Library cost|Anti-infection Compound Library solubility dmso|Anti-infection Compound Library purchase|Anti-infection Compound Library manufacturer|Anti-infection Compound Library research buy|Anti-infection Compound Library order|Anti-infection Compound Library mouse|Anti-infection Compound Library chemical structure|Anti-infection Compound Library mw|Anti-infection Compound Library molecular weight|Anti-infection Compound Library datasheet|Anti-infection Compound Library supplier|Anti-infection Compound Library in vitro|Anti-infection Compound Library cell line|Anti-infection Compound Library concentration|Anti-infection Compound Library nmr|Anti-infection Compound Library in vivo|Anti-infection Compound Library clinical trial|Anti-infection Compound Library cell assay|Anti-infection Compound Library screening|Anti-infection Compound Library high throughput|buy Antiinfection Compound Library|Antiinfection Compound Library ic50|Antiinfection Compound Library price|Antiinfection Compound Library cost|Antiinfection Compound Library solubility dmso|Antiinfection Compound Library purchase|Antiinfection Compound Library manufacturer|Antiinfection Compound Library research buy|Antiinfection Compound Library order|Antiinfection Compound Library chemical structure|Antiinfection Compound Library datasheet|Antiinfection Compound Library supplier|Antiinfection Compound Library in vitro|Antiinfection Compound Library cell line|Antiinfection Compound Library concentration|Antiinfection Compound Library clinical trial|Antiinfection Compound Library cell assay|Antiinfection Compound Library screening|Antiinfection Compound Library high throughput|Anti-infection Compound high throughput screening| (n=6 per group): (i) APP mice alone were given distilled water, (ii) APP donepezil mice were treated with donepezil (0.92mg/kg/d),

and (iii-v) APP mice treated with GEPT low dose (0.75g/kg/d), middle dose (1.5g/kg/d), and large dose (3.0g/kg/d) for 8 months. Three-month-old-male C57BL/6J mice (n=6) for vehicle were given distilled water for 8 months. Immunohistochemistry and Western blot analysis were used in determining amyloid precursor protein ( APP), A beta 1-42, BACE1, PS1, IDE and NEP in hippocampal CA1 region and hippocampal tissue homogenates. Results: Expression level of A beta 1-42 in the large GEPT dose was significantly click here lower than those in APP alone or APP treated

with donepezil, and decreased to the level of vehicle mice. Similarly, a ratio calculated from the densitometric measures of A beta 1-42 protein/beta-actin in the large dose also was significantly lower than those in APP mice alone or APP mice treated with donepezil, and even reduced to the level of vehicle mice. Expression of PS1 in the large GEPT dose was significantly lower than that of APP mice alone and decreased to those in vehicle mice as well. A decreased level of BACE1 appeared, respectively, in APP mice treated with the large GEPT dose or donepezil but was still much greater than the level of vehicle mice. In contrast, NEP and IDE showed a significantly higher expression in APP mice treated with either the large dose or the middle dose of GEPT compared to APP mice alone or donepezil, and were even increased in level compared to vehicle mice. Conclusion: The combination of GEPT extracts can reduce levels of endogenous A beta peptide in APPV717I transgenic mice through the inhibition of PS1 activity rather than BACE1 and the promotion of IDE and NEP activity. Lower-expression of PS1 and over-expression of IDE or NEP may be helpful in potentially lowering brain A beta levels in subjects with AD, and hence GEPT appears to offer potential that should be explored in AD.