• Preventive Nutrition and Food Science
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• 제19권4호
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• pp.343-347
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• 2014

The present study investigated the effects of Vaccinium uliginosum L. (bilberry) on the learning and memory impairments induced by amyloid-${\beta}$ protein ($A{\beta}P$) 1-42. ICR Swiss mice were divided into 4 groups: the control ($A{\beta}40$-1A), control with 5% bilberry group ($A{\beta}40$-1B), amyloid ${\beta}$ protein 1-42 treated group ($A{\beta}1$-42A), and $A{\beta}1$-42 with 5% bilberry group ($A{\beta}1$-42B). The control was treated with amyloid ${\beta}$-protein 40-1 for placebo effect, and Alzheimer's disease (AD) group was treated with amyloid ${\beta}$-protein 1-42. Amyloid ${\beta}$-protein 1-42 was intracerebroventricular (ICV) micro injected into the hippocampus in 35% acetonitrile and 0.1% trifluoroacetic acid. Although bilberry added groups tended to decrease the finding time of hidden platform, no statistical significance was found. On the other hand, escape latencies of $A{\beta}P$ injected mice were extended compared to that of $A{\beta}40$-1. In the Probe test, bilberry added $A{\beta}1$-42B group showed a significant (P<0.05) increase of probe crossing frequency compared to $A{\beta}1$-42A. Administration of amyloid protein ($A{\beta}1$-42) decreased working memory compared to $A{\beta}40$-1 control group. In passive avoidance test, bilberry significantly (P<0.05) increased the time of staying in the lighted area compared to AD control. The results suggest that bilberry may help to improve memory and learning capability in chemically induced Alzheimer's disease in experimental animal models.

• 생약학회지
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• 제38권4호
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• pp.308-311
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• 2007

Inhibition of acetylcholinesterase and amyloid beta(1-42) peptide is good drug targets for Alzheimer's disease therapeutics. Among the twenty enthusiasm reducing herbals, the 70% methanol extracts (1 mg/ml) of Moutan Radicis Cortex and Forsythiae Fructus showed 91.5% and 85.3% about acethylcholinesterase inhibition, respectively. The extracts (1 mg/ml) of Coptidis Rhizoma and Paeoniae Radix Rubra showed more than 85% inhibition rate against amyloid beta (1-42) peptide aggregation. The neuroprotective effect of the extracts (1 mg/ml) of Moutan Radicis Cortex, Forsythiae Fructus and Paeoniae Radix Rubra showed 90.0%, 87.4% and 85.1% to compare with amyloid beta (1-42) peptide treated cells (IMR-32), respectively. Three herbs, Moutan Radicis Cortex, Forsythiae Fructus and Paeoniae Radix Rubra are promising candidates from natural products for development of Alzheimer's disease therapeutics.

• EDISON SW 활용 경진대회 논문집
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• 제3회(2014년)
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• pp.237-249
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• 2014

Deposition of amyloid-${\beta}$ ($A{\beta}$) proteins is the conventional pathological hallmark of Alzheimer's disease (AD). The $A{\beta}$ protein formed from the amyloid precursor protein is predominated by the 40 residue protein ($A{\beta}40$) and by the 42 residue protein ($A{\beta}42$). While $A{\beta}40$ and $A{\beta}42$ differ in only two amino acid residues at the C-terminal end, $A{\beta}42$ is much more prone to aggregate and exhibits more neurotoxicity than $A{\beta}40$. Here, we investigate the molecular origin of the difference in the aggregation propensity of these two proteins by performing fully atomistic, explicit-water molecular dynamics simulations. Then, it is followed by the solvation thermodynamic analysis based on the integral-equation theory of liquids. We find that $A{\beta}42$ displays higher tendency to adopt ${\beta}$-sheet conformations than $A{\beta}40$, which would consequently facilitate the conversion to the ${\beta}$-sheet rich fibril structure. Furthermore, the solvation thermodynamic analysis on the simulated protein conformations indicates that $A{\beta}42$ is more hydrophobic than $A{\beta}40$, implying that the surrounding water imparts a larger thermodynamic driving force for the self-assembly of $A{\beta}42$. Taken together, our results provide structural and thermodynamic grounds on why $A{\beta}42$ is more aggregation-prone than $A{\beta}40$ in aqueous environments.

• 공업화학
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• 제30권3호
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• pp.379-383
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• 2019

The capability of detecting amyloid beta 42 ($A{\beta}42$), a biomarker of Alzheimer's disease, using a thiolated protein A-functionalized bimetallic surface plasmon resonance (SPR) chip was investigated. An optimized configuration of a bimetallic chip containing gold and silver was obtained through calculations in the intensity measurement mode. The surface of the SPR bimetallic chip was functionalized with thiolated protein A for the immobilization of $A{\beta}42$ antibody. The response of the thiolated protein A-functionalized bimetallic chip to $A{\beta}42$ in the concentration range of 50 to 1,000 pg/mL was linear. Compared to protein A without thiolation, the thiolated protein A resulted in greater sensitivity. Therefore, the thiolated protein A-functionalized bimetallic SPR chip can be used to detect very low concentrations of the biomarker for Alzheimer's disease.

• Journal of Microbiology and Biotechnology
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• 제27권11호
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• pp.2044-2051
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• 2017

The main pathological hallmark of Alzheimer's disease is the deposition of amyloid-beta ($A{\beta}$) peptides in the brain. $A{\beta}$ has been widely used to mimic several aspects of Alzheimer's disease. However, several characteristics of amyloid-induced Alzheimer's disease pathology are not well established, especially in mice. The present study aimed to develop a new Alzheimer's disease model by investigating how $A{\beta}$ can be effectively aggregated using prokaryotes and eukaryotes. To express the $A{\beta}42$ complex in HEK293 cells, we cloned the $A{\beta}42$ region in a tandem repeat and incorporated the resulting construct into a eukaryotic expression vector. Following transfection into HEK293 cells via lipofection, cell viability assay and western blotting analysis revealed that exogenous $A{\beta}42$ can induce cell death and apoptosis. In addition, recombinant His-tagged $A{\beta}42$ was successfully expressed in Escherichia coli BL21 (DE3) and not only readily formed $A{\beta}$ complexes, but also inhibited the proliferation of SH-SY5Y cells and E. coli. For in vivo testing, recombinant His-tagged $A{\beta}42$ solution ($3{\mu}g/{\mu}l$ in $1{\times}PBS$ containing $1mM\;Ni^{2+}$) was injected stereotaxically into the left and right lateral ventricles of the brains of C57BL/6J mice (n = 8). Control mice were injected with $1{\times}PBS$ containing $1mM\;Ni^{2+}$ following the same procedure. Ten days after the sample injection, the Morris water maze test confirmed that exogenous $A{\beta}$ caused an increase in memory loss. These findings demonstrated that $Ni^{2+}$ is capable of complexing the 50-kDa amyloid and that intracerebroventricular injection of $A{\beta}42$ can lead to cognitive impairment, thereby providing improved Alzheimer's disease models.

• Nutrition Research and Practice
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• 제8권4호
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• pp.386-390
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• 2014

BACKGROUND: Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity. MATERIALS/METHODS: We investigated the effects of ADA extract on two mouse models of Alzheimer's disease (AD); intracerebroventricular injection of ${\beta}$-amyloid peptide ($A{\beta}$) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice. RESULTS: Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of $A{\beta}1$-42 until evaluation) effectively blocked $A{\beta}1$-42-induced impairment in passive avoidance performance, and $A{\beta}1$-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-$1{\alpha}$ in the hippocampus. In addition, it alleviated the $A{\beta}1$-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-$1{\beta}$ in the brain. CONCLUSIONS: The results of this study suggest that ADA stem extract may be useful for prevention and treatment of AD.

• Journal of Ginseng Research
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• 제37권1호
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• pp.100-107
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• 2013

This study examined the effect of fermented ginseng (FG) on memory impairment and ${\beta}$-amyloid ($A{\beta}$) reduction in models of Alzheimer's disease (AD) in vitro and in vivo. FG extract was prepared by steaming and fermenting ginseng. In vitro assessment measured soluble $A{\beta}42$ levels in HeLa cells, which stably express the Swedish mutant form of amyloid precursor protein. After 8 h incubation with the FG extract, the level of soluble $A{\beta}42$ was reduced. For behavioral assessments, the passive avoidance test was used for the scopolamine-injected ICR mouse model, and the Morris water maze was used for a transgenic (TG) mouse model, which exhibits impaired memory function and increased $A{\beta}42$ level in the brain. FG extract was treated for 2 wk or 4 mo on ICR and TG mice, respectively. FG extract treatment resulted in a significant recovery of memory function in both animal models. Brain soluble $A{\beta}42$ levels measured from the cerebral cortex of TG mice were significantly reduced by the FG extract treatment. These findings suggest that FG extract can protect the brain from increased levels of $A{\beta}42$ protein, which results in enhanced behavioral memory function, thus, suggesting that FG extract may be an effective preventive or treatment for AD.

• Biomolecules & Therapeutics
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• 제14권2호
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• pp.106-109
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• 2006

Neprilysin (Nep) is known to be important to degrade $A{\beta}$ derived from amyloid precursor protein (APP) by cleavage with $\beta-and\;\gamma$-secretases. In order to determine whether a correspondence between $A{\beta}-42/{\gamma}-secretase$ activity and Nep levels exists in postnatal aging of transgenic mice expressing either neuron-specific enolase (NSE)-controlled human mutant presenilin-2 (hPS2m) or APPsw alone, the levels of Nep expression and $A{\beta}-42/{\gamma}-secretase$ activity were examined age of 5, 12, and 20 months, respectively. The levels of Nep expression in both types of transgenic brains were decreased relative to those of control mice in a aging-related manner, while the level of $A{\beta}-42/{\gamma}-secretase$ activity was reversibly increased. Thus, changes in $A{\beta}-42$ may all reflect variation in amounts of Nep enzyme.

• 생약학회지
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• 제46권4호
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• pp.327-333
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• 2015

Alzheimer's disease (AD) is a progressive neurodegenerative disorder symptomatically characterized by impairment in memory and cognitive abilities. AD is characterized pathologically by the deposition of ${\beta}$-amyloid ($A{\beta}$) peptides of 40-42 residues, which are generated by processing of amyloid precursor protein (APP). $A{\beta}$ has been believed to be neurotoxic and now is also considered to have a role on the mechanism of memory dysfunction. In this study, we tested that EtOH extract of the fruits of Chaenomeles sinensis Koehne (CSE) affects on the processing of APP from the APPswe over-expressing Neuro2a cell line. We found that CSE increased over 2 folds of the $sAPP{\alpha}$ secretion level, a metabolite of ${\alpha}$-secretase. We showed that CSE reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ by down regulation of ${\beta}$-secretase (BACE) without cytotoxicity. Furthermore, we found that CSE inhibited BACE and acetylcholinesterase activity in vitro. We suggest that Chaenomelis Fructus may be an useful source to develop a herbal medicine for AD.

• 약학회지
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• 제50권5호
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• pp.326-331
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• 2006

We designed and synthesized new benzylpiperidinyl ether derivatives as beta-amyloid aggregation inhibitors for the development of novel anti-Alzheimer's disease agents. As starting material, 4-hydroxypiperidine was used. For protection of the amine group in piperidine (2), di-tert-butyl dicarbonate was reacted with 4-hydroxypiperidine in the presence of triethylamine. For introduction of benzyl group, benzylbromide was treated with compound 2 in dioxane. After deprotection of Boc group on amine in compound 3, ester (5) was synthesized by addition of ethyl-4-chlorobutyrate. The alcohol 6 was synthesized by hydride reduction of 5 using $LiAlH_4$. To obtain final products (7-14), the alcohol 6 was condensed with each of substituted benzoic acids. To screen beta-amyloid aggregation inhibition of the products, thioflavinT assay was performed using $A{\beta}1-42\;at\;37^{\circ}C$ for 26 h incubation, in vitro. From the result of screening, compound 8, 9, 11 and 12 showed effective activity about $65{\sim}85\;{\mu}M\;as\;IC_{50}$ value. Among the prepared compounds, 4-[4-(benzyloxy)piperidino]butyl-4-chlorobenzoate (8) was the most effective inhibitor having $IC_{50}\;of\;65.4{\mu}M$.