• Archives of Pharmacal Research
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• v.28 no.11
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• pp.1275-1281
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• 2005

The $G_{q/11}$ protein-coupled receptors, such as muscarinic (M1 & M3) receptors, have been shown to regulate the release of a soluble amyloid precursor protein (sAPP$\alpha$) produced from $\alpha$-secretase processing. However, there is no direct evidence for the precise characteristics of G proteins, and the signaling mechanism for the regulation of $G_{q/11}$ protein-coupled receptor mediated sAPP$\alpha$ release is not clearly understood. This study examined whether the muscarinic receptor-mediated release of sAPP$\alpha$ is directly regulated by $G\alpha_{q/11}$ proteins. The HEK293 cells were transiently cotransfected with muscarinic M3 receptors and a dominant-negative minigene construct of the G protein $\alpha$ subunit. The sAPP$\alpha$ release in the media was measured using an antibody specific for sAPP. The sAPP$\alpha$ release enhancement induced by muscarinic receptor stimulation was decreased by a $G_{q/11}$ minigene construct, whereas it was not blocked by a control minigene construct (the G$\alpha$ carboxy peptide in random order, G$\alpha_{q}$R) or $G\alpha_{j}$ constructs. This indicated a direct role of the $G\alpha_{q/11}$ protein in the regulation of muscarinic M3 receptor-mediated sAPP$\alpha$ release. We also investigated whether the transactivation of the epidermal growth factor receptor (EGFR) by a muscarinic agonist could regulate the sAPP$\alpha$ release in SH-SY5Y cells. Pretreatment of a specific EGFR kinase inhibitor, tyrophostin AG1478 (250 nM), blocked the EGF-stimulated sAPP$\alpha$ release, but did not block the oxoM­stimulated sAPP$\alpha$ release. This demonstrated that the transactivation of the EGFR by muscarinic receptor activation was not involved in the muscarinic receptor-mediated sAPP$\alpha$ release.

• Journal of Information Technology Applications and Management
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• v.29 no.6
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• pp.43-62
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• 2022

As the used trading market grows centered on online platforms, it is evolving from practical consumption to pursuing various forms of consumption value. Consumers purchase rare products, enjoy the transaction itself with consumers with the same preference, and investment or eco-friendly value consumption is also increasing. In this regard, the transaction of the second-hand transaction app service must have sincerity in order to respond to various consumption values. In addition, it is necessary to study what components the second-hand trading app service should aim for to secure authenticity and how the usefulness and ease of second-hand trading apps affect the relationship. The research used a questionnaire method to test hypotheses and surveyed 215 consumers in their 20s, 30s, and 40s who had purchased used clothing online within a year. Among them, 200 responses, excluding outliers, were statistically analyzed using SPSS 21.0 and AMOS 22.0 as confirmatory factor analysis and structural equation models. This study aims to determine the effect of the authenticity of the online used trading app service on the satisfaction of the used trading app service. To this end, based on the previous research results, the following research hypotheses were established and verified statistically. First, the authenticity of the online used trading app service will significantly impact the satisfaction of the used trading app service. Second, the usefulness of the used trading app service will have a moderating effect on the effect of the authenticity of the used trading app service on the satisfaction of the used trading app service. Third, the ease of the used trading app service will have a moderating effect on the authenticity of the used trading app service on the satisfaction of the used trading app service. As a result of the study, the authenticity of the used trading app service significantly affected the satisfaction of the used trading app service. Appeared to be The results of this study will help understand used transaction app services where consumption of used products occurs from the viewpoint of product circular use behavior and can be used as a strategic plan to promote the use of used transaction apps in the future.

• BMB Reports
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• v.49 no.6
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• pp.337-343
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• 2016

Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer's disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of autophagy for degradation of pathogenic molecules in neurodegenerative diseases. Deletion of KFERQ in APP increased C-terminal fragments (CTFs) and secreted N-terminal fragments of APP and kept it away from lysosomes. KFERQ deletion did not abolish the interaction of APP or its cleaved products with heat shock cognate protein 70 (Hsc70), a protein necessary for CMA or microautophagy. These findings suggest that KFERQ motif is important for normal processing and degradation of APP to preclude the accumulation of APP-CTFs although it may not be important for CMA or microautophagy.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.229-233
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• 2010

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.

• Journal of Korea Society of Industrial Information Systems
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• v.27 no.2
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• pp.143-161
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• 2022

This study examines the effect of used trading app's consumption value and protection motivation and the perceived usefulness and continuous use intention. The proposed research model and developed hypotheses were tested using structural equations modeling based on data collected from 293 customers with experience in used transaction app's. The results of the study confirm the positive effects of the used trading app's consumption value and protection motive theory is perceived usefulness of customer. In addition, there is a positive relationship between a customer's perceived usefulness and continuous use intention of used trading app's. The study provides On a theoretical level valuable insights into the sustainability of transaction app's after post-COVID 19 and the importance of developing used trading app's consumption value and protection motivation, but there is also a limitation that the region is limited.

• Journal of Information Technology Services
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• v.13 no.3
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• pp.51-76
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• 2014

As the smart phone devices gain popularity, companies no longer consider mobile application marketing as an auxiliary marketing tactic. The branded mobile application (branded app) becomes an important part of marketing strategies. This study is an attempt to investigate antecedents of the use intention of the branded app from the perspective of TAM (Technology Acceptance Model). This study takes a macro perspective in explaining the adoption process by incorporating a set of new, yet promising additional variables into the TAM model such as flow experience, benefits, innovation inclination, and customization features. Data were collected by using a survey research. A total of 270 responses were collected. Questionnaires from 25 individuals were removed from the data set due to the insincere responses, leaving the final sample size of 245. Findings support all but one hypotheses of the study. Both perceived utilitarian benefits and customization features of the branded app were found to have positive influences on the perceived usefulness of the branded app. Also, the innovation inclination and perceived entertainment of branded app users showed positive influences on the perceived ease of use of branded app. In addition, it was shown that the perceived usefulness about the use of the branded app influenced positively the flow experience and the users' attitudes toward branded app. Also, the ease of use perceived by branded app users had positive influences on the perceived usefulness and the user's attitude toward branded app. However, the ease of use of branded app did not have a significant influence on the flow experience among users. Moreover, the flow experience from the use of branded app users influenced positively the user's attitude toward branded app. Finally, the users' attitudes toward branded app had positive influences on their intention to use the branded app. Implications for practitioners and academicians are provided.

• Journal of Information Technology Applications and Management
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• v.26 no.3
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• pp.99-120
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• 2019

The purpose of this study is to provide information necessary for establishing a new strategy for customer service improvement by deriving factors affecting user satisfaction and continuous use intention of mobile app service user characteristics, system characteristics, and social characteristics. The results of this study are summarized as follows. First, reliability, innovation, familiarity, convenience, and self-efficacy among the characteristics of mobile app are analyzed as factors that have the greatest influence on user's perceived usefulness. Second, convenience, mobility, and visibility are some of the characteristics of mobile app service. Third, identity, security, and expectation agreement among mobile app service characteristics are analyzed as negative factors that do not affect users' perceived usefulness. Fourth, interactivity, familiarity, and self-efficacy among the characteristics of mobile app service were analyzed as positive factors that have the greatest effect on user's perceived ease of use. Fifth, reliability, mobility, visibility, and convenience among mobile app service characteristics are analyzed as factors that have some positive effects on perceived ease of use of app users. Sixth, identity, innovation, and security among the characteristics of mobile app service are negatively influenced by mobile app users' perceived ease of use. Seventh, the perceived usefulness of mobile app users is analyzed as a factor that has a very positive effect on user satisfaction. Eighth, the perceived ease of use of mobile app users is analyzed as a factor affecting perceived usefulness positively. Ninth, the perceived ease and expectation of mobile app users are positively influenced on user satisfaction. The tenth, the perceived usefulness of the mobile app users was analyzed as a factor having a very positive influence on the persistent intention to use. For the eleventh, the perceived ease of use of mobile app users was analyzed as a factor having a positive effect on the persistent intention to use. The twelfth, mobile app user satisfaction was analyzed as a factor having a very positive effect on the persistent intention to use.

• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.276-282
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• 2019

${\beta}$-amyloid precursor protein (APP) can be cleaved by ${\alpha}$-, and ${\gamma}$-secretase at plasma membrane producing soluble ectodomain fragment ($sAPP{\alpha}$). Alternatively, following endocytosis, APP is cleaved by ${\beta}$-, and ${\gamma}$-secretase at early endosomes generating ${\beta}$-amyloid ($A{\beta}$), the main culprit in Alzheimer's disease (AD). Thus, APP endocytosis is critical for $A{\beta}$ production. Recently, we reported that Monsonia angustifolia, the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased $A{\beta}$ production. In this study, we examined the underlying mechanism of justicidin A, the active compound of M. angustifolia, on $A{\beta}$ production. We found that justicidin A reduced endocytosis of APP, increasing $sAPP{\alpha}$ level, while decreasing $A{\beta}$ level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on $A{\beta}$ production was blocked by endocytosis inhibitors, indicating that the decreased APP endocytosis by justicidin A is the underlying mechanism. Thus, justicidin A, the active compound of M. angustifolia, may be a novel agent for AD treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.53-57
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• 2004

In order to evaluate the neuroprotective effects of Kamisinsunbulo-dan(KSM), the cytotoxicity of amyloid β and the recovering effect of KSM were checked at first. Then the viability of C6 cells was tested in comparison with each concentration of KSM. The cytotoxicity of amyloid β(31-35) showed from 5 μM higher to 100 μM. And the recovering effect by KSM showed significantly at 100㎍/㎖. concentration. And the cell viability was shown significantly over 200 ㎍/㎖ of KSM. This is thought that the viability has some relation to length of culturing duration, 6 to 12 hrs. Lastly in the western blotting of APP, the amount of low molecule's APP was decreased. So the APP form ratio(APPr) changed to increase, and it meant that KSM can be used to lower the toxic APP, and can be a candidate for Alzheimer's disease.

• Environmental Mutagens and Carcinogens
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• v.25 no.1
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• pp.19-24
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• 2005

The Swedish double mutation (KM670/671NL) of amyloid precursor protein (Swe-APP) is associated with early-onset familial Alzheimer's disease (FAD) and increases amyloid beta peptide production. Although APP/A/3 mediated neurotoxicity is observed both in vitro and in vivo, the relationship between mutant APP expression, A/3 production, and neuronal death observed in the brains of FAD patients remains to be elucidated. In this study, we investigated the mechanisms of Swe-APP-induced cell death in HEK293 and NGF-differentiated PC 12 cells. We found that the expression of Swe-APP induced cytochrome C relase, activation of caspase 3 in HEK 293 and NGF-differentiated PC 12 cells. We also show that the reactive oxygen species (ROS) was detected in Swe-APP expressing HEK 293 cells and NGF-differentiated PC 12 cells and that pretreatment with vitamine E attenuated the cellular death, cytochrome C release induced by Swe-APP expression, indicating the involvement of free radical in these processes. These results suggest one of possible apoptotic mechanisms of Swe-APP which could occur through cytochrome C release from mitochondria and this apoptosis inducing effects could be at least in part, due to ROS generation by Swe-APP expression.