• Proceedings of the PSK Conference
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• 2003.04a
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• pp.204.1-204.1
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• 2003

Azheimer's Disease (AD) known as senile dementia accounts for 50％ of all dementia cases and is in growing status as population goes up. Generally. AD is a progressive neurodegenerative disease and includes much of senile plaque in cerebral hippocampus and cortex in patient's brain. For decades. AD theory is explained by amyloid cascade hypothesis. In process of the hypothesis, amyloid hypothesis forms fibrillar form beta-amyloid peptide (A${\beta}$ peptide) and extraordinarily accumulates in brain tissue, and lastly senile plaque is formed, which pathologically affect the brain. (omitted)

• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.108-112
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• 2009

Alzheimer's disease(AD) is a neurodegenerative disorder characterized pathologically by senile plaques, neurofibrillary tangles, and synapse loss. Especially, extracellular beta-amyloid (Abeta) deposition is a major pathological hallmark of Alzheimer's disease (AD). In AD senile plaques, high level of iron and car-bonylated Abeta were detected. Iron has a Lewis acid property which can increase the electrophilicity of carbonyls, which may react catalytically with nucleophiles, such as amines. Hence, this study investigated whether or not iron could promote the carbonylation of amine with malondialdehyde (MDA) in the physiological condition. As the basic study, we examined that iron might promote the conjugation reaction between propylamine, monoamine molecule and MDA in the physiological condition. As the concentration of iron increased, the fluorescence intensity produced from the conjugation reaction increased in a dose-dependent manner. Instead of propylamine, we applied the same reaction condition to Abeta 1-40 peptide, one of major components founded in AD senile plaques for the conjugation reaction. As the result, the fluorescence intensity produced from the conjugation reaction between Abeta 1-40 peptide and MDA showed the similar trend to that of the reaction used with propylamine. This study suggests that iron can accelerate the conjugation reaction of MDA to Abeta 1-40 peptide and play an another important role in deterioration of AD brain.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.202.1-202.1
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• 2003

Microglial cell can act for phagocytosis against abnormal particles in brain, which means that beta-amyloid produced from APP(amyloid precursor protein) can be phagocytosed by microglia when released. In contrast. when senile plaque has already been formed in brain cortex and hippocamphal region, microglia can also accelerate the AD pathogenesis due to chronic inflammatory action, which lead to neuron cell cytotoxicity. (omitted)

• Fisheries and Aquatic Sciences
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• v.21 no.5
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• pp.13.1-13.8
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• 2018

Amyloid plaque, also called senile plaque, the product of aggregation of ${\beta}$-amyloid peptides ($A{\beta}$), is observed in brains of the patients with Alzheimer's disease (AD) and is one of the key factors in etiology of the disease. In this study, hydrolysates obtained from the sea hare (Aplysia kurodai) were investigated for ${\beta}$-secretase inhibitory peptide. The sea hare's muscle protein was hydrolyzed using six enzymes in a batch reactor. Trypsin hydrolysate had highest ${\beta}$-secretase inhibitory activity compared to the other hydrolysates. ${\beta}$-secretase inhibitory peptide was separated using Sephadex G-25 column chromatography and high-performance liquid chromatography on a C18 column. ${\beta}$-secretase inhibitory peptide was identified as eight amino acid residues of Val-Ala-Ala-Leu-Met-Leu-Phe-Asn by N-terminal amino acid sequence analysis. $IC_{50}$ value of purified ${\beta}$-secretase inhibitory peptide was $74.25{\mu}M$, and Lineweaver-Burk plots suggested that the peptide purified from sea hare muscle protein acts as a competitive inhibitor against ${\beta}$-secretase. Results of this study suggest that peptides derived from sea hare muscle may be beneficial as anti-dementia compounds in functional foods or as pharmaceuticals.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.04a
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• pp.123-135
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• 2006

Alzheimer's disease (AD) is the most common form of dementia in the aging population and is clinically characterized by a progressive loss of cognitive abilities. Pathologically, it is defined by the appearance of senile plaques - extracellular insoluble, congophilic protein aggregates composed of amyloid $\beta$ (A$\beta$) and neurofibrillary tangles (NFTs) - inyracellular lesions consisting of paired helical filaments from hyperphosphorylated cytoskeletal tau protein as described by Alois Alzheimer a century ago. These hallmarks still serve as the major criteria for a definite diagnosis of the disease. Consequently, one of the key strategy for drug development in this disease area focuses on reducing the concentration of cerebral A$\beta$ plaque by using substances that inhibit A$\beta$ fibril formation. We focused on developing inhibitors by synthesizing several kinds of aromatic molecules. The synthetic compounds were initially screened to evaluate the effective compound by tioflavin T fluorescence assay. The selected effective compounds were tested cytotoxicity and protective effect from A$\beta$-induced neuronal toxicity by cell based MTT assay with HT22 hippocampal neurons. The BBB permeability on effectors was also tested in in vitro co-culture model(HUVEC/C6 cell line). The behavior test wea carried out in mutant APP/PS1 transgenic mouse model of Alzheimer's disease. And inhibition of A$\beta$ fibril formation by the effective compound was monitored with transmitted electron microscopic images.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.136.1-136.1
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• 2003

$\beta$-amyloid (A$\beta$) peptide produced from amyloid precursor protein (APP) is a major cause of Alzheimer's disease (AD). Therefore, in early phase of AD, imbalance of the production and the clearance of $A\beta$ is regarded as an important factor to progressive AD presenting senile plaque, a hallmark of AD. In the present study, we wanted to verify whether Rg3 can playa role in helping microglia engulfing $A\beta$ peptides. Validations for the study was conducted by using DiI-Ac-LDL, which attached only on type A macrophage scavenger receptor (MSR-A) and ligands for he receptor, fucoidan. (omitted)

• Molecules and Cells
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• v.40 no.9
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• pp.613-620
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• 2017

The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid ${\beta}-peptide$ ($A{\beta}$) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than $A{\beta}$ plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD. A growing amount of evidence suggests that soluble $A{\beta}$ oligomers in concert with hyperphosphorylated tau (pTau) serve as the major pathogenic drivers of neurodegeneration in AD. Increased $A{\beta}$ oligomers trigger neuronal dysfunction and network alternations in learning and memory circuitry prior to clinical onset of AD, leading to cognitive decline. Furthermore, accumulated damage to mitochondria in the course of aging, which is the best-known nongenetic risk factor for AD, may collaborate with soluble $A{\beta}$ and pTau to induce synapse loss and cognitive impairment in AD. In this review, I summarize and discuss the current knowledge of the molecular and cellular biology of AD and also the mechanisms that underlie $A{\beta}-mediated$ neurodegeneration.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.3
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• pp.317-321
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• 2014

Amyloid-${\beta}$ protein ($A{\beta}$) is a pathological component of Alzheimer's disease (AD) by participating in the senile plaque formation in the patient's brain. Although the exact mechanism of $A{\beta}$ toxicity is not fully elucidated, it is considered to be closely related to its fibrillation process. For prevention of AD, recent studies have suggested various small molecules which inhibit $A{\beta}$ fibrillation. In this report, ${\beta}$-asarone found in acorus plant has been investigated as an anti-amyloid molecule. ${\beta}$-Asarone was demonstrated to prevent in vitro fibrillation of $A{\beta}$ by inducing the oligomer formation that obviously decreased cytotoxicity. Therefore, ${\beta}$-asarone could be suggested as an inhibitory agent of $A{\beta}$ fibrillation and toxicity, which would help us not only to understand underlying principle of amyloidogenesis mechanism but also to develop a controlling strategy toward AD.

• Korean Journal of Pharmacognosy
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• v.49 no.2
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• pp.182-187
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• 2018

Many plant derived phytochemicals have been considered as the main therapeutic strategy against Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder, and the most predominant cause of dementia in the elderly. Cholinergic deficit, senile plaque/${\beta}$-amyloid ($A{\beta}$) peptide deposition and oxidative stress have been identified as three main pathogenic pathways which contribute to the progression of AD. We screened many different plant species for their effective use in both modern and traditional system of medicines. In this study, we tested that MeOH extract of the stem bark of Hopea chinensis (Merr.) Hand.-Mazz. (HCM) affects on the processing of Amyloid precursor portein (APP) from the APPswe over-expressing Neuro2a cell line. We showed that HCM reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ in a dose dependent manner. We found that HCM increased over 1.5 folds of the secretion level of $sAPP{\alpha}$, a metabolite of ${\alpha}$-secretase. Furthermore, we found that HCM inhibited acetylcholinesterase activity in vitro. We suggest that the stem bark of Hopea chinensis may be a useful source to develop a therapeutics for AD.

• Bulletin of the Korean Chemical Society
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• v.25 no.6
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• pp.838-842
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• 2004

Amyloid peptide (A${\beta}$) is the major component of senile plaques found in the brain of patient of Alzheimer's disease. ${\beta}$-amyloid peptide (25-35) (A${\beta}$25-35) is biologically active fragment of A${\beta}$. The three-dimensional structure of A${\beta}$25-35 in aqueous solution with 50% (vol/vol) TFE determined by NMR spectroscopy previously adopts an ${\alpha}$-helical conformation from $Ala^{30}$ to $Met^{35}$. It has been proposed that A${\beta}$(25-35) exhibits pH- and concentration-dependent ${\alpha}-helix{\leftrightarrow}{\beta}$sheet transition. This conformational transition with concomitant peptide aggregation is a possible mechanism of plaque formation. Here, in order to gain more insight into the mechanism of ${\alpha}$-helix formation of A${\beta}$25-35 peptide by TFE, which particularly stabilizes ${\alpha}$-helical conformation, we studied the secondary-structural elements of A${\beta}$25-35 peptide by molecular dynamics simulations. Secondary structural elements determined from NMR spectroscopy in aqueous TFE solution are preserved during the MD simulation. TFE/water mixed solvent has reduced capacity for forming hydrogen bond to the peptide compared to pure water solvent. TFE allows A${\beta}$25-35 to form bifurcated hydrogen bonds to TFE as well as to residues in peptide itself. MD simulation in this study supports the notion that TFE can act as an ${\alpha}$-helical structure forming solvent.