• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.689-696
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• 2018

Increasing evidence implicates changes in $[Ca^{2+}]_i$ and oxidative stress as causative factors in amyloid beta ($A{\beta}$)-induced neuronal cell death. Cyanidin-3-glucoside (C3G), a component of anthocyanin, has been reported to protect against glutamate-induced neuronal cell death by inhibiting $Ca^{2+}$ and $Zn^{2+}$ signaling. The present study aimed to determine whether C3G exerts a protective effect against $A{\beta}_{25-35}$-induced neuronal cell death in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague-Dawley rats using MTT assay for cell survival, and caspase-3 assay and digital imaging methods for $Ca^{2+}$, $Zn^{2+}$, MMP and ROS. Treatment with $A{\beta}_{25-35}$ ($20{\mu}M$) for 48 h induced neuronal cell death in cultured rat pure hippocampal neurons. Treatment with C3G for 48 h significantly increased cell survival. Pretreatment with C3G for 30 min significantly inhibited $A{\beta}_{25-35}$-induced $[Zn^{2+}]_i$ increases as well as $[Ca^{2+}]_i$ increases in the cultured rat hippocampal neurons. C3G also significantly inhibited $A{\beta}_{25-35}$-induced mitochondrial depolarization. C3G also blocked the $A{\beta}_{25-35}$-induced formation of ROS. In addition, C3G significantly inhibited the $A{\beta}_{25-35}$-induced activation of caspase-3. These results suggest that cyanidin-3-glucoside protects against amyloid ${\beta}$-induced neuronal cell death by reducing multiple apoptotic signals.

• YAKHAK HOEJI
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• v.54 no.6
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• pp.529-534
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• 2010

Alzheimer's disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}$-amyloid ($A{\beta}$) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. $A{\beta}$ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. Recently, we investigated that a quinoline compound from natural product reduced the secretion of $A{\beta}$ from the neuroblastoma N2a cells (NL/N cell line) overexpressing APPswe. In this study, 3-phenyl-1-isoquinolinamine, a synthetic isoquinoline compound was analyzed to determine its effects on the metabolism of APP. It inhibited the secretion of $A{\beta}$ peptides from the N2a NL/N cell line. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependent manner. Immunoblotting study showed that it inhibited APP stabilization and expression and it slightly increased the stablization and the expression of ${\gamma}$-secreatase component from the N2a NL/N cell line. We suggest that 3-phenyl-1-isoquinolinamine inhibits APP metabolism and $A{\beta}$ generation by the means of BACE inhibitory mechanism. This is the first report that 3-phenyl-1-isoquinolinamine inhibits the secretion of $A{\beta}$ peptides from neuroblastoma cells.

• Korean Journal of Medicinal Crop Science
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• v.16 no.6
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• pp.409-415
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• 2008

Moutan cortex, the root bark of Paeonia suffruticosa Andrews (Paeoniaceae), has pharmacological effects such as anti-inflammatory, antiallergic, analgesic and antioxidant activities. We investigated a methanol extract of Moutan cortex for neuroprotective effects on neurotoxicity induced by amyloid ${\beta}$ protein ($A{\beta}$) (25-35) in cultured rat cortical neurons. Exposure of cultured cortical neurons to $10\;{\mu}M\;A{\beta}$ (25-35) for 24 h induced neuronal apoptotic death. Moutan cortex inhibited $10\;{\mu}M\;A{\beta}$ (25-35)-induced neuronal cell death at 30 and $50\;{\mu}g/m{\ell}$, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. Moutan cortex inhibited $10\;{\mu}M\;A{\beta}$ (25-35)-induced elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), and generation of reactive oxygen species (ROS) which were measured by fluorescent dyes. Moutan cortex also inhibited glutamate release into medium induced by $10\;{\mu}M\;A{\beta}$ (25-35), which was measured by HPLC. These results suggest that Moutan cortex prevents $A{\beta}$ (25-35)-induced neuronal cell damage by interfering with the increase of $[Ca^{2+}]_i$, and then inhibiting glutamate release and ROS generation. Moutan cortex may have a therapeutic role in preventing the progression of Alzheimer's disease.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.191-191
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• 2002

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.94-94
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• 2002

• Bulletin of the Korean Chemical Society
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• v.22 no.10
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• pp.1065-1066
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• 2001

• Environmental Analysis Health and Toxicology
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• v.19 no.3
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• pp.279-286
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• 2004

Although numerous studies have shown that cadmium disturbs the normal biological processes in central nervous system, the mechanism of toxicity is not well understood. The present study has investigated the effect of cadmium on oxidative stress, Na$^{+}$K$^{+}$ ATPase activity and the aggregation of amyloid beta peptide ($\beta$-amyloid) in neuronal cell line, HT22 cell. LC$_{5}$ and LC$_{50}$ of cadmium for HT22 cell resulted from MTT assay was 4.1 uM and 9.5 uM, respectively. Cadmium (2 to 8 uM) dose-dependently increased the lipid peroxidation and decreased the content of glutathione. Cadmium 4 uM showed a significant decrease in Na$^{+}$/K $^{+}$ ATPase activity as compared with control group. The aggregation of $\beta$-amyloid was accelerated in a dose-dependent manner by the treatment with 2 to 8 uM cadmium. These results suggest that the neurotoxicity of cadmium can be mediated by the increase in oxidative stress and decrease in Na$^{+}$/K$^{+}$ ATPase activity.se activity.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.90-96
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• 2011

Automated HPLC/SPE/HPLC coupling experiments using the Sepbox system allowed the rapid identification of four bioactive principles reducing the production of amyloid $\beta$-peptide ($A{\beta}$) from two South African plants, Euclea crispa subsp. crispa and Crinum macowanii. The structures of biologically active compounds isolated from the methanol extract of Euclea crispa subsp. crispa were assigned as 3-oxo-oleanolic acid (1) and natalenone (2) based on their NMR and MS data, while lycorine (3) and hamayne (4) were isolated from the dichloromethane-methanol (1:1) extract of Crinum macowanii. These compounds were shown to inhibit the production of $A{\beta}$ from HeLa cells stably expressing Swedish mutant form of amyloid precursor protein (APPsw).

• Journal of the Korean Society of Radiology
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• v.10 no.5
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• pp.307-312
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• 2016

Alzheimer's disease is the most common degenerative brain diseases that causes dementia. ${\beta}$-amyloid neuritic plaque density that accumulates in the brain is difficult to perform daily living, such as memory loss, language ability deterioration. It is used to estimate ${\beta}$-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive impairment. Using the $^{18}F$-Florbetaben with high sensitivity and specificity for the ${\beta}$-amyloid neuritic plaque density to evaluate the usefulness for the early diagnosis of Alzheimer's disease. In $^{18}F$-FDG Brain imaging shows no specific findings. And it appeared on the MR-Brain imaging without atrophy of the hippocampus. However, the intake of ${\beta}$-amyloid neuritic plaque density in $^{18}F$-Florbetaben informs that it is the progress of Alzheimer's disease. Therefore, $^{18}F$-Florobetaben is very useful for early diagnosis of Alzheimer's disease.

• Journal of Sensor Science and Technology
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• v.21 no.5
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• pp.339-344
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• 2012

This article describes a novel method for the detection of amyloid-${\beta}$($A{\beta}$) peptide that utilizes a photo-sensitive field-effect transistor (p-FET). According to a recent study, $A{\beta}$ protein has been known to play a central role in the pathogenesis of Alzheimer's disease (AD). Accordingly, we investigated the variation of photo current generated from p-FET with and without intracellular magnetic beads conjugated with $A{\beta}$ peptides, which are placed on the p-FET sensing areas. The decrease of photo current was observed due to the presence of the magnetic beads on the channel region. Moreover, a similar characteristic was shown when the Raw 264 cells take in magnetic beads treated with $A{\beta}$ peptide. This means that it is possible to simply detect a certain protein using magnetic beads and a p-FET device. Therefore, in this paper, we suggest that our method could detect tiny amounts of $A{\beta}$ for early diagnosis of AD using the p-FET devices.