• Journal of the Korean Chemical Society
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• v.58 no.6
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• pp.553-559
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• 2014

Alzheimer's disease (AD) is a devastating neurodegenerative disease that represents the most common form of dementia among the elderly population. The deposition of aggregated ${\beta}$-amyloid ($A{\beta}$) senile plaques in the human brain is a classic observation in the neuropathology of AD, yet an understanding of the mechanism of their formation remains elusive. $A{\beta}$ is formed through endoproteolysis of the amyloid precursor protein (APP) by ${\beta}$-secretase (BACE1, ${\beta}$-site APP-cleaving enzyme) and ${\gamma}$-secretase. In this study, BACE1 protein was successfully over-expressed, purified, and refolded and utilized in a binding study with hispidin. We developed a simpler refolding method using a urea gradient and size-exclusion gel filtration to purify an active BACE1 protein variant, in larger quantities than that reported previously, and measured the binding affinity of hispidin to the BACE1 protein variant through isothermal titration calorimetry.

• The Korea Journal of Herbology
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• v.29 no.6
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• pp.73-83
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• 2014

Objectives : This study was investigated the effects of the root of Polygala tenuifolia (POL) on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Methods : Chronic cerebral hypoperfusion was produced by permanent bilateral common carotid artery occlusion (pBCAO). POL was administered orally once a day (130 mg/kg of water-extract) for 28 days starting at 4 weeks after the pBCAO. The acquisition of learning and the retention of memory were tested on 9th week after the pBCAO using the Morris water maze. In addition, effects of POL on $A{\beta}$ generation and expressions of APP and BACE1 were observed in the hippocampus of rats. Results : POL significantly prolonged the swimming time spent in target quadrant and significantly reduced the swimming time spent in the quadrant far from the target. POL significantly increased the percentage of swim in the targer quadrant in the retention test, while POL was not effective on the escape latencies in the acquisition training trials. POL significantly reduced the levels of $A{\beta}_{(1-40)}$ and $A{\beta}_{(1-42)}$ in the cerebral cortex and the level of $A{\beta}_{(1-42)}$ in the hippocampus produced by chronic cerebral hypoperfusion. POL also significantly attenuated the up-regulation of APP and BACE1 expression in the hippocampus produced by chronic cerebral hypoperfusion. Conclusions : The results show that POL alleviated memory deficit and up-regulation of $A{\beta}$ and BACE1 expressions in the hippocampus. This result suggests that POL may exert ameliorating effect on memory deficit through inhibition of ${\beta}$-secretase activity and $A{\beta}$ generation.

• Molecules and Cells
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• v.39 no.7
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• pp.543-549
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• 2016

MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neuro-degenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, ${\beta}$-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.

• Preventive Nutrition and Food Science
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• v.16 no.1
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• pp.18-23
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• 2011

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuronal loss and extracellular senile plaques containing $\beta$-amyloid peptide (A$\beta$). The deposition of the A$\beta$ peptide following proteolytic processing of amyloid precursor protein (APP) by $\beta$-secretase (BACE1) and $\gamma$-secretase is a critical feature in the progression of AD. Among the plant extracts tested, the ethanol extract of Petasites japonicus leaves showed novel protective effect on B103 neuroblastoma cells against neurotoxicity induced by A$\beta$, as well as a strong suppressive effect on BACE1 activity. Ethanol extracts of P. japonicus leaves were sequentially extracted with methylene chloride, ethyl acetate and butanol and evaluated for potential to inhibit BACE1, as well as to suppress A$\beta$-induced neurotoxicity. Exposure to A$\beta$ significantly reduced cell viability and increased apoptotic cell death. However, pretreatment with ethyl acetate fraction of P. japonicus leaves prior to A$\beta$ (50 ${\mu}M$) significantly increased cell viability (p<0.01). In parallel, cell apoptosis triggered by A$\beta$ was also dramatically inhibited by ethyl acetate fraction of P. japonicus leaves. Moreover, the ethyl acetate fraction suppressed caspase-3 activity to the basal level at 30 ppm. Taken together, these results demonstrated that P. japonicus leaves appear to be a useful source for the inhibition and/or prevention of AD by suppression of BACE1 activity and attenuation of A$\beta$ induced neurocytotoxicity.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.50 no.1
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• pp.85-91
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• 2017

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of insidious onset that causes gradual loss of memory and cognitive function, and it is the most common form of dementia in the elderly. AD is characterized by neuritic plaques and neurofibrillary tangles in the brain, together with loss of neuronal cells. The major neuropathological hallmark of AD is the accumulation of extracellular neurotoxic ${\beta}-amyloid$ ($A{\beta}$) peptides, such as $A{\beta}1-42$, in the brain. In the present study, we investigated the effect of sargachromenol (SCM), sargaquinoic acid (SQA) and sargahydroquinoic acid (SHQA) isolated from Sargassum serratifoilum ethanol extract (SSE) on $A{\beta}$ production in vitro using APP751-transfected Chinese hamster ovary cells (CHO-751). CHO-751 cells were treated with various concentrations of SSE, SCM, SQA and SHQA, and the level of extracellular $A{\beta}1-42$ was evaluated by enzyme-linked immunosorbent assay. SSE and SHQA reduced the production of $A{\beta}1-42$ in CHO-751 cells. Therefore, SHQA isolated from S. serratifolium has potential as an inhibitor of neurotoxic $A{\beta}$ peptide production.

• Journal of Plant Biotechnology
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• v.47 no.4
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• pp.283-288
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• 2020

Although the evolution of Arabidopsis thaliana and humans diverged approximately 1.6 billion years ago, recent studies have demonstrated that protein function and cellular processes involved in disease response remain remarkably conserved. Particularly, γ-secretase, a multisubunit protein complex that participates in intramembrane proteolysis (RIP) regulation, is also known to mediate the cleavage of more than 80 substrates including the amyloid precursor protein (APP) and the Notch receptor. Although the genes (PS1/2, APH-1, PEN-2, and NCT) coding for the γ-secretase complex components are present in plant genomes, their function remains largely uncharacterized. Given that the deposition of 42 amino acid long amyloid-β peptides (hAβ₄₂) is thought to be one of the main causes of Alzheimer's disease, we aimed to examine the physiological effects of hAβ₄₂ peptides on plants. Interestingly, we found that Arabidopsis protoplast death increased after 24 h of exposure to 3 or 5 µM hAβ₄₂ peptides. Furthermore, transgenic Arabidopsis plants overexpressing the hAβ₄₂ gene exhibited changes in primary root length and silique phyllotaxy. Taken together, our results demonstrate that hAβ₄₂ peptides, a metazoan protein, significantly affect Arabidopsis protoplast viability and plant morphology.

• Korean Journal of Veterinary Service
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• v.45 no.1
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• pp.47-54
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• 2022

Subcutaneous abscesses, which occur mainly in goats and sheep, are lymph node abscesses caused by Corynebacterium pseudotuberculosis infection, and are divided into internal, external, and mixed types depending on the type of occurrence. While diagnostic methods for subcutaneous abscesses have been continuously studied, research reports for effective treatment and management of subcutaneous abscesses are inadequate. Therefore, this study was conducted to determine the changes in biometric information related to the inflammatory markers of goats induced by subcutaneous abscesses by infection with C. pseudotuberculosis. For this, hematological tests, analysis of inflammatory indicators, and analysis of serum proteins through electrophoresis separation of goats with healthy goats and goats inoculated with C. pseudotuberculosis to induce subcutaneous abscesses were compared and analyzed by date, and the differences and characteristics were identified periodically. As a result, in goats induced with subcutaneous abscesses, anemia findings related to a rapid decrease in red blood cell (RBC), hematocrit (HCT), and hemoglobin (Hb) were observed, and a significant increase in inflammatory cells expressed in total white blood cell (WBC), neutrophil, and monocytes was observed. And the levels of acute phase protein (APP) such as fibrinogen, haptoglobin, and serum amyloid A (SAA) were observed to increase rapidly immediately after infection. In addition, in the results of electrophoretic analysis of serum proteins, it was observed that the levels of α-globulin and β-globulin were significantly increased in goats with subcutaneous abscesses. That is, when looking at these changes, it was found that the systemic inflammatory response of goats was rapidly induced immediately after infection with the C. pseudotuberculosis pathogen. Through this study, it was possible to identify changes in the biomarkers of goats with subcutaneous abscesses, which had not been reported. Furthermore, these analyzed data are thoughts to be of great help in identifying, treating, and managing the goats of subcutaneous abscesses.

• Korean Journal of Food Science and Technology
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• v.53 no.3
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• pp.278-289
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• 2021

The rapid aging of society has led to a surge in cognitive dysfunction in the elderly. As there is limited evidence for the development of dementia in medicine, a shift in focus on prevention strategies using bioactive compounds in food is required. This systematic review evaluated the effects of various bioactive compounds on age-associated cognitive decline. The literature was searched for terms related to bioactive compounds in cognitive decline and article selection was limited to clinical randomized controlled trials for a single bioactive compound. We identified 21 studies that evaluated the strength of the evidence. ω-3 fatty acids and vitamin B presented a strong evidence level, whereas vitamin D and E, anserine/carnosine, and chromium were defined as having moderate levels of evidence. ω-3 fatty acids relieved cognitive decline and reduced amyloid β-related protein accumulation. Vitamin B decreased homocysteine levels, which is accompanied by alleviation of cognitive function. In conclusion, ω-3 and vitamin B have the potential to improve age-associated cognitive decline.