• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.139-140
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• 2003

• BMB Reports
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• v.43 no.10
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• pp.656-663
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• 2010

Amyloid precursor protein (APP), which is critically involved in the pathogenesis of Alzheimer's disease (AD), is cleaved by gamma/epsilon-secretase activity and results in the generation of different lengths of the APP Intracellular C-terminal Domain (AICD). In spite of its small size and short half-life, AICD has become the focus of studies on AD pathogenesis. Recently, it was demonstrated that AICD binds to different intracellular binding partners ('adaptor protein'), which regulate its stability and cellular localization. In terms of choice of adaptor protein, phosphorylation seems to play an important role. AICD and its various adaptor proteins are thought to take part in various cellular events, including regulation of gene transcription, apoptosis, calcium signaling, growth factor, and $NF-{\kappa}B$ pathway activation, as well as the production, trafficking, and processing of APP, and the modulation of cytoskeletal dynamics. This review discusses the possible roles of AICD in the pathogenesis of neurodegenerative diseases including AD.

• Korean Journal of Pharmacognosy
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• v.38 no.4
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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.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.253-264
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• 2006

Object: This research investigated effects of Jujadokseo-hwan on mice with Alzheimer's Disease induced by $amyloid-{\beta}$. According to Dongyibogam, Jujadokseo-hwan can cure amnesia. Amyloid-B is believed to induce oxidative stress and inflammation in the brain, postulated to play important roles in the pathogenesis of Alzheimer's disease. In this way $Amyloid-{\beta}$ induces Alzheimer's Disease. Methods : In order to make an efficient prescription and cope with dementia, learning and memory functions of mice were tested on passive avoidance test and V-maze task. $NF-{\kappa}B$ were measured from protein derived from the brain. RT-PCR was done for !gene analysis. Primers were protein kinase Band $NGF-{\alpha}$. Results : 1. Jujadokseo-hwan was effective for memory capacity on passive avoidance test. but noneffective for spatial memory capacity and locomotor activity on Y -maze task. 2. The measurement of $NF-{\kappa}B$ showed upward tendancies and the result of RT-PCR showed up-regulation when given Jujadokseo-hwan by mouth. Conclusion: Results suggest that Jujadokseo-hwan is effective on mice with Alzheimer's Disease induced by $amyloid-{\beta}$.

• Bulletin of the Korean Chemical Society
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• v.35 no.2
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• pp.425-430
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• 2014

Amyloidogenic proteins often exhibit fibrillar polymorphism through alternative assembly processes, which has been considered to have possible pathological implications. Here, firefly luciferase (LUC) is shown to induce amyloid polymorphism of ${\alpha}$-synuclein, the major constituent of Lewy bodies found in Parkinson's disease, by acting as a novel template. The drastically accelerated fibrillation kinetics of ${\alpha}$-synuclein with LUC required the nucleation center produced by the active enzyme of LUC. Fluorescent dye binding, transmission electron microscopy, and Fourier transformed infrared spectroscopy revealed the morphologically distinctive amyloid fibrils of ${\alpha}$-synuclein prepared in the absence or presence of LUC. As the altered morphological characteristics became inherent to the mature fibrils, those properties were inherited to next-generations via nucleation-dependent fibrillation process. The seed control, therefore, would be an effective means to modify amyloid fibrils with different biochemical characteristics. In addition, the LUC-directed amyloid fibrillar polymorphism also suggests that other cellular biomolecules including enzymes in general are able to diversify amyloid fibrils, which could be self-propagated with diversified biological activities, if any, inside cells.

• 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.

• Biomedical Science Letters
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• v.25 no.1
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• pp.7-14
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• 2019

Alzheimer's disease (AD) is highly prevalent in dementia, with no specifically effective treatment having yet been discovered. Amyloid plaques are one of the key hallmarks of AD. Transgenic mouse models exhibiting Alzheimer's disease-like pathology have been widely used to study the pathophysiology of Alzheimer's disease. In this study, we showed an age-dependent correlation between cognitive function, pathological findings, and [F-18] Florbetaben (FBB) PET images. Nineteen transgenic mice (12 with AD, 7 with controls) were used for this study. We observed an increase in ${\beta}$-Amyloid deposition ($A{\beta}$) in brain tissue and [F-18] FBB amyloid PET imaging in the AD group. The [F-18] FBB data showed a mildly negative trend with cognitive function. Pathological findings were negatively correlated with cognitive functions. These finding suggests that amyloid beta deposition can be well-monitored with [F-18] FBB PET and a decline in cognitive function is related to the increase in amyloid plaque burden.

• Journal of Oriental Neuropsychiatry
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• v.21 no.2
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• pp.191-200
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• 2010

Objectives : This experiment was designed to investigate the effect of Chongmyung-Tang Prescription Combination(CmTP-$C_{1-10}$) extract on the production of amyloid $\beta$ protein and $\beta$-site amyloid precursor protein-cleaving enzyme(BACE) activity. Methods : The effect of CmTP-$C_{1-10}$ extract on expression of APP mRNA, BACE2 mRNA in BV2 microglia cell line treated by lipopolysacchride(LPS) and amyloid $\beta$ protein fragment(A$\beta$ fragment) were investigated. The effect of CmTP-$C_{1-10}$ extract on production of amyloid $\beta$ protein(A$\beta$) in BV2 microglia cell line treated by LPS and A$\beta$ fragment were investigated. The effect of CmTP-$C_{1-10}$ extract on BACE activity were investigated. Results : 1. CmTP-$C_9$ extract the most significantly suppressed the expression of APP mRNA, BACE2 mRNA in BV2 microglia cell line treated by LPS and A$\beta$ fragment. 2. CmTP-$C_9$ extract significantly suppressed the production of A$\beta$ in BV2 microglia cell line treated by LPS and A$\beta$ fragment. 3. CmTP-$C_9$ extract the most significantly inhibited BACE activity. Conclusions : These results suggest that CmTP-$C_9$ may be effective for the prevention and treatment of Alzheimer's Disease. Investigation into clinical use of CmTP-$C_9$ for Alzheimer's Disease is suggested for future research.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.11
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• pp.115-120
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• 2019

This study was undertaken to determine the correlation between β-amyloid, serum lipid levels, and cognitive function in the elderly with mild Alzheimer's dementia. The study was conducted in December 2018, enrolling 45 elderly people with mild Alzheimer's disease. Blood analysis measured the β-amyloid and serum lipid levels, and cognitive function was measured using MMSE-K. The correlation between β-amyloid, serum lipid levels and cognitive function was determined using Pearson's correlation analysis. A significantly negative correlation was observed between the β-amyloid level and cognitive function (p<0.05). Furthermore, serum lipid levels and cognitive function also revealed a significantly negative correlation between TC and LDL levels (p<0.05). These results indicate that increasing levels of β-amyloid, TC, and LDL augments a negative correlation that decreases the cognitive function, signifying that management of pathologic factors related to dementia is important for the prevention and improvement of cognitive function in dementia patients.

• Bulletin of the Korean Chemical Society
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• v.28 no.12
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• pp.2283-2287
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• 2007

Amyloid fibril formation of amyloid β/A4 protein (Aβ) is critical to understand the pathological mechanism of Alzheimer's disease and develop controlling strategy toward the neurodegenerative disease. For this purpose, dequalinium (DQ) has been employed as a specific modifier for Aβ aggregation and its subsequent cytotoxicity. In the presence of DQ, the final thioflavin-T binding fluorescence of Aβ aggregates decreased significantly. It was the altered morphology of Aβ aggregates in a form of the bundles of the fibrils, distinctive from normal single-stranded amyloid fibrils, and the resulting reduced β-sheet content that were responsible for the decreased fluorescence. The morphological transition of Aβ aggregates assessed with atomic force microscope indicated that the bundle structure observed with DQ appeared to be resulted from the initial multimeric seed structure rather than lateral association of preformed single-stranded fibrils. Investigation of the seeding effect of the DQ-induced Aβ aggregates clearly demonstrated that the seed structure has determined the final morphology of Aβ aggregates as well as the aggregative kinetics by shortening the lag phase. In addition, the cytotoxicity was also varied depending on the final morphology of the aggregates. Taken together, DQ has been considered to be a useful chemical probe to control the cytotoxicity of the amyloid fibrils by influencing the seed structures which turned out to be central to develop therapeutic strategy by inducing the amyloid fibrils in different shapes with varied toxicities.