• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.04a
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• pp.109-120
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• 2006

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathological hallmarks of AD are senile plaques and neurofibrillary tangles in the brain. Major component of senile plaques is amyloid beta peptide(A$\beta$) which is derived from amyloid precursor protein (APP). A$\beta$ is generated through the sequential cleavage of App by $\beta$ - and $\gamma$-secretases. $\beta$-secretase excises the ectodomain of APP ($\beta$-APPs) to leave a 99-amino acid long C-terminal fragment (APP-C99-CTF) in the membrane. $\gamma$-secretase then cleaves this membrane-tethered APP-CTF within the transmembrane domain, so releasing A$\beta$ peptides and APP-intracellular domain (AICD). Thus, $\beta$- and $\gamma$-secretase are regarded to perform the key steps in the pathogenesis of AD and have become important therapeutic targets in the prevention and treatment of AD. Enormous efforts have been focused to develop the amyloid beta related drug for cure of AD becuase A$\beta$ is believed to be one of the major causes of AD. since major pharmaceutical companies in world wide base compete to develop new drug for AD, we have to be careful to choose the drug target to success the tough race. In the present talk, possible drug targets based on basic research results will be discussed. These molecules should be a good target for development of new drug for AD and be less competitive to have a good shape for world wide competition.

• Molecules and Cells
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• v.26 no.3
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• pp.291-298
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• 2008

Human karyopherin ${\beta}3$, highly homologous to a yeast protein secretion enhancer (PSE1), has often been reported to be associated with a mediator of a nucleocytoplasmic transport pathway. Previously, we showed that karyopherin ${\beta}3$ complemented the PSE1 and KAP123 double mutant. Our research suggested that karyopherin beta has an evolutionary function similar to that of yeast PSE1 and/or KAP 123. In this study, we performed yeast two-hybrid screening to find a protein which would interact with karyopherin ${\beta}3$ and identified apolipoprotein A-I (apo A-I), a secretion protein with a primary function in cholesterol transport. By using in vitro binding assay, co-immunoprecipitation, and colocalization studies, we defined an interaction between karyopherin ${\beta}3$ and apo A-I. In addition, overexpression of karyopherin ${\beta}3$ significantly increased apo A-I secretion. These results suggest that karyopherin ${\beta}3$ plays a crucial role in apo A-I secretion. These findings may be relevant to the study of a novel function of karyopherin ${\beta}3$ and coronary artery diseases associated with apo A-I.

• Toxicological Research
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• v.17
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• pp.47-57
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• 2001

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and its pathology is characterized by the presence of numerous numbers of senile plaques and neurofibrillary tangles. Several genetic and transgenic studies have indicated that excess amount of $\beta$-amyloid protein (A$\beta$) is produced by mutations of $\beta$TEX>$\beta$-amyloid precursor protein and causes learning impairment. Moreover, $A\beta$ has a toxic effect on cultured nerve cells. To prepare AD model animals, we have examined continuous (2 weeks) infusion of $A\beta$ into the cerebral ventricle of rats. Continuous infusion of $A\beta$ induces learning impairment in water maze and passive avoidance tasks, and decreases choline acetyltransferase activity in the frontal cortex and hippocampus. Immunohistochemical analysis revealed diffuse depositions of $A\beta$ in the cerebral cortex and hippocampus around the ventricle. Furthermore, the nicotine-evoked release of acetylcholine and dopamine in the frontal cortex/hippocampus and striatum, respectively, is decreased in the $A\beta$-infused group. Perfusion of nicotine (50 $\mu\textrm{M}$) reduced the amplitude of electrically evoked population spikes in the CA1 pyramidal cells of the control group, but not in those of the $A\beta$-infused group, suggesting the impairment of nicotinic signaling in the $A\beta$-infused group. In fact, Kd, but not Bmax, values for ［$^3H$］ cytisine binding in the hippocampus significantly increased in the $A\beta$-infused rats. suggesting the decrease in affinity of nicotinic acetylcholine receptors. Long-term potentiation (LTP) induced by tetanic stimulations in CA1 pyramidal cells, which is thought to be an essential mechanism underlying learning and memory, was readily observed in the control group, whereas it was impaired in the $A\beta$-infused group. Taken together, these results suggest that $A\beta$ infusion impairs the signal transduction mechanisms via nicotinic acetylcholine receptors. This dysfunction may be responsible, at least in part, for the impairment of LTP induction and may lead to learning and memory impairment. We also found the reduction of glutathione- and Mn-superoxide dismutase-like immunoreactivity in the brains of $A\beta$-infused rats. Administration of antioxidants or nootropics alleviated learning and memory impairment induced by $A\beta$ infusion. We believe that investigation of currently available transgenic and non-transgenic animal models for AD will help to clarify the pathogenic mechanisms and allow assessment of new therapeutic strategies.

• The Journal of Internal Korean Medicine
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• v.19 no.2
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• pp.381-391
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• 1998

The present study was done to investigate the effects of Bombusae concretio Salicea (BCS) on cultured astrocyte cell system and lipid peroxidation in $A{\beta}25-35$ treatment conditions. Cell killing was significantly enhanced by addition of increasing concentrations of $A{\beta}25-35$. Pretreatment of BCS attenuated in cell killing enhanced by increasing concentrations of $A{\beta}25-35$. MDA level induced by $A{\beta}25-35$ treatment was significantly increased and the level was slightly reduced by pretreatment of BCS. The present study showed that $A{\beta}25-35$ strongly increased MDA level and the level was enhanced by addition of increasing concentrations of In conclusion, it was shown that $A{\beta}25-35$ is not only potent lipid peroxide inducer, but also cause protection of neurodegeneration induced by $A{\beta}25-35$. It can be concluded that the activation of antioxidative enzymes may be related to the inhibition of lipid peroxidative reactions. We cannot fully explain to effects of BCS at present; however, the ability of BCS to reduce cell killing and MDA level induced by $A{\beta}25-35$ suggest that BCS may be a protective agent for free radical generating compounds such as $A{\beta}25-35$.

• Nuclear Engineering and Technology
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• v.31 no.4
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• pp.401-407
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• 1999

We have performed two experiments in the fast critical assembly BFS to measure the effective delayed neutron fraction $\beta$$_{eff}$ values and compared the results to validate the $\beta$$_{eff}$ computation code, BETA-K. Measurements of $\beta$$_{eff}$ were carried out in a metallic plutonium core and a metallic uranium core with Cf$^{252}$ source pseudo-reactivity method. Fission integrals and correction factors, which were used to obtain the experimental $\beta$$_{eff}$ values, were calculated by using the LMR core design computation code system of KAERI. BETA-K has been developed consistently with the hexagonal Nodal Expansion Method (NEM) and it used delayed neutron data of ENDF/B-VI. By comparing the computed $\beta$$_{eff}$ values with the measured ones, we found that the results from BETA-K agreed with the experimental values within the experimental error bound.ror bound.

• Korean Journal of Food Science and Technology
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• v.31 no.3
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• pp.644-650
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• 1999

A normal and a waxy hull-less barley with similar ${\beta}-glucan$ contents were selected, and the effects of ${\beta}-glucans$ on rheological and pasting properties were investigated by using their flour extracts and isolated ${\beta}-glucan$ gum materials. ${\beta}-Glucans$ in the barley cultivars were extracted in a crude form with alkaline extraction, and the waxy hull-less barley produced more ${\beta}-glucan$ gum yield. The waxy barley also showed higher viscosities of water and alkaline flour extracts, compared to the normal barley. Both normal and waxy barley ${\beta}-glucan$ gums exhibited pseudoplastic flow behavior, and increasing ${\beta}-glucan$ concentration increased viscosity in a similar manner. The normal barley flour had a higher amylograph peak viscosity than did waxy barley flour. On the other hand, waxy barley flour with treatment of $HgCl_2$ demonstrated considerably higher increase in peak viscosity. Pasting characteristics of normal and waxy barley starches in the presence of ${\beta}-glucan$ gum solutions were tested using a rapid visco-analyzer (RVA). ${\beta}-Glucan$ gums increased the pasting viscosities of the barley starches, and the synergistic increase in viscosity appeared to be higher in the normal barley starch.

• Journal of Microbiology and Biotechnology
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• v.12 no.5
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• pp.813-818
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• 2002

Expression of monokine induced by IFN-$\gamma$(Mig) mRNA is well-known to strictly depend on Interferon-$\gamma$(IFN-$\gamma$). Lipopolysaccharide (LPS) alone Is weakly effective on Mig mRNA expression in mouse Peritoneal macrophages. This study was undertaken to investigate the synergistic effect of LPS and IFN-$\beta$ on chemokine Mig gene expression in mouse peritoneal macrophages. Although IFN-$\beta$ alone was minimally effective, LPS plus IFN-$\beta$ synergized to produce a high level of Mig mRNh. The synergistic effect of LPS and IFN-$\beta$ (LPS/IFN-$\beta$) on Mig mRNA expression was strain-specific. The most effective synergistic effect of LPS/IFN-$\beta$ on the mRNh expression was found in simultaneous stimulation of LPS/IFN-$\beta$. This synergy was modulated at the level of the gene transcription and was not dependent on a new protein synthesis. Synergistic effect of LPS/IFN-$\beta$ also required the activation of $NF-_KB$. Accordingly, these data suggest that LPS/IFN-$\beta$ synergizes the expression of Mig mRNA through a process that depends on a pretranscriptional level and/or coincident Mig mRNA transcription.

• YAKHAK HOEJI
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• v.52 no.6
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• pp.494-499
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• 2008

The role of antibody in the fungal infections is controversial. However, our previous reports showed a certain epitope in Candida albicans cell wall (CACW) induces protective antibody. A major problem is that the epitope isolation requires tremendous time with high cost. This aspect led us to investigate a simple way inducing protective antibodies against C. albicans. In the present study, we determined if $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) from Glabrae Radix (a family of Leguminosae) has immunoadjuvant activity. Data displayed that the $18{\beta}$-GA suppressed proliferations of both T- and Blymphocytes at high concentrations, whereas below 20 ${\mu}M$ concentration the compound supported the proliferations. These observations indicate that $18{\beta}$-GA has immunoregulatory activity. Based on this observation, an immunoadjuvant effect was examined at the low concentration. Results from animal experiments showed that CACW combined with or without $18{\beta}$-GA produced the anti-C. albicans antiserum in mice. Nevertheless, the CACW combined with $18{\beta}$-GA formula only protected mice against disseminated candidiasis (P<0.05). These data implicate that $18{\beta}$-GA has immunoadjuvant activity, which may provoke the CACW antigen to induce protective antibody. Currently, we are investigating possible mechanism of how the $18{\beta}$-GA provokes such protective immunity against the disseminated disease.

• Applied Biological Chemistry
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• v.43 no.2
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• pp.136-140
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• 2000

Two steroidal saponins were isolated from MeOH extract of the rhizomes of Asparagus oligoclonos. Using the spectroscopic techniques of $^1H,\;^{13}C$ NMR and 2D NMR, they were identified as $3-O-[{\beta}-D-glucopyranosyl-(1{\rightarrow}2)-{\beta}-D-glucopyranosyl]-(25S)-spirostan-3{\beta}-ol$ and $3-O-{{\beta}-D-glucopyranosyl-(1{\rightarrow}2)-[{\beta}-D-xylopyranosyl-(1{\rightarrow}4)]-{\beta}-D-glucopyranosyl}-(25S)-spirostan-3{\beta}-ol$, respectively. They were first isolated from A. oligoclonos. The in vitro antibacterial activities as well as antibacterial spectrums against 20 bacteria strains were investigated with MIC test. Both saponins inhibited the growth of 10 bacteria strains at the concentration of$100\;{\mu}g/ml$.

• Journal of Integrative Natural Science
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• v.6 no.3
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• pp.125-137
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• 2013

Promising evidence suggests that amyloid beta peptide ($A{\beta}$), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signalling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in $A{\beta}$-induced apoptosis of non-neuronal cells, including cerebral endothelial cells, astrocytes and oligodendrocytes, is mitochondrial dysfunction. The apoptosis signalling cascade upstream of mitochondria entails $A{\beta}$ activation of neutral sphingomyelinase, resulting in the release of ceramide from membrane sphingomyelin. Ceramide then activates protein phosphatase 2A (PP2A), a member in the ceramide-activated protein phosphatase (CAPP) family. PP2A dephosphorylation of Akt and FKHRL1 plays a pivotal role in $A{\beta}$-induced Bad translocation to mitochondria and transactivation of Bim. Bad and Bim are pro-apoptotic proteins that cause mitochondrial dysfunction characterized by excessive ROS formation, mitochondrial DNA (mtDNA) damage, and release of mitochondrial apoptotic proteins including cytochrome c, apoptosis inducing factor (AIF), endonuclease G and Smac. The cellular events activated by $A{\beta}$ to induce death of non-neuronal cells are complex. Understanding these apoptosis signalling processes will aid in the development of more effective strategies to slow down age-dependent cerebrovascular degeneration caused by progressive cerebrovascular $A{\beta}$ deposition.