• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.115-115
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• 2001

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.172.2-172.2
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• 2000

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.219.1-219.1
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• 2000

• Annals of Clinical Neurophysiology
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• v.23 no.1
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• pp.65-67
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• 2021

• BMB Reports
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• v.50 no.12
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• pp.634-639
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• 2017

We aimed to assess the anti-inflammatory and antioxidative properties of KHG26792, a novel azetidine derivative, in amyloid ${\beta}$ ($A{\beta}$)-treated primary microglial cells. KHG26792 attenuated the $A{\beta}-induced$ production of inflammatory mediators such as IL-6, $IL-1{\beta}$, $TNF-{\alpha}$, and nitric oxide. The levels of protein oxidation, lipid peroxidation, ROS, and NADHP oxidase enhanced by $A{\beta}$ were also downregulated by KHG26792 treatment. The effects of KHG26792 against the $A{\beta}-induced$ increases in inflammatory cytokine levels and oxidative stress were achieved by increasing the phosphorylation of $Akt/GSK-3{\beta}$ signaling and by decreasing the $A{\beta}-induced$ translocation of $NF-{\kappa}B$. Our results provide novel insights into the use of KHG26792 as a potential agent against $A{\beta}$ toxicity, including its role in the reduction of inflammation and oxidative stress. Nevertheless, further investigations of cellular signaling are required to clarify the in vivo effects of KHG26792 against $A{\beta}-induced$ toxicity.

• Molecules and Cells
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• v.27 no.6
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• pp.651-656
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• 2009

The formation of ${\beta}$-amyloid peptide ($A{\beta}$) is initiated from cleavage of amyloid precursor protein (APP) by a family of protease, ${\alpha}$-, ${\beta}$-, and ${\gamma}$-secretase. Sub W, a substrate peptide, consists of 10 amino acids, which are adjacent to the ${\beta}$-cleavage site of wild-type APP, and Sub M is Swedish mutant with double mutations on the left side of the ${\beta}$-cleavage site of APP. Sub W is a normal product of the metabolism of APP in the secretary pathway. Sub M is known to increase the efficiency of ${\beta}$-secretase activity, resulting in a more specific binding model compared to Sub W. Three-dimensional structures of Sub W and Sub M were studied by CD and NMR spectroscopy in water solution. On the basis of these structures, interaction models of ${\beta}$-secretase and substrate peptides were determined by molecular dynamics simulation. Four hydrogen bonds and one water-mediated interaction were formed in the docking models. In particular, the hydrogen bonding network of Sub M-BACE formed spread over the broad region of the active site of ${\beta}$-secretase (P5-P3'), and the side chain of P2- Asn formed a hydrogen bond specifically with the side chain of Arg235. These are more favorable to the cleavage of Sub M by ${\beta}$-secretase than Sub W. The two substrate peptides showed different tendency to bind to ${\beta}$-secretase and this information may useful for drug development to treat and prevent Alzheimer's disease.

• The Korean Journal of Food And Nutrition
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• v.30 no.6
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• pp.1279-1285
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• 2017

$Amyloid-{\beta}$ protein ($A{\beta}$) is known to increase free radical production in neuronal cells, leading to cell death by oxidative stress. The purpose of this study was to evaluate the protective effects of $PineXol^{(R)}$ on $A{\beta}_{25-35}$ induced neuronal cell death. Rat pheochromocytoma (PC-12) cells were pre-treated with $100{\mu}g/mL$ of $PineXol^{(R)}$ for 2 h. The cells were exposed to single dose of $30{\mu}M$ $A{\beta}_{25-35}$ for 24 h. Cell death was assessed by a cell count kit-8 (CCK-8) assay, lactate and dehydrogenase (LDH) release assay. An Apoptotic process was analyzed by a protein expression of the Bcl-2 family using western blotting. Cell viability increased in PC-12 cells treated with both $A{\beta}_{25-35}$ and $PineXol^{(R)}$, compared to the control group. $PineXol^{(R)}$ induced a decrease of the Bcl-2 protein expression (p<0.05), while Bax and Sod1 increased (p<0.05), indicating attenuation of $A{\beta}_{25-35}$ induced apoptosis. These results suggest that $PineXol^{(R)}$ may be a good candidate for the prevention of Alzheimer's disease(AD).

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.62-70
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• 2001

Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques (SPs) and neurofibrillary tangles(NFTs). ${\beta}$-amyloid protein($A{\beta}$) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of $A{\beta}$ and tau formation are thought to be a final common pathway of AD. Acetylcholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and ${\alpha}$-macroglobulin increase risk of AD. In this article, we will review about the neurobiology of AD and some newly developed research areas.

• Journal of Oriental Neuropsychiatry
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• v.12 no.2
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• pp.157-171
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• 2001

Astrocytes are glial cells that play a major role in the inflammation observed in Alzheimer's disease (AD). Upon stimulation from various agents, these cells adopt a reactive phenotype, a morphological hallmark in AD pathology, during which they themselves may produce still more inflammatory cytokines. Substance P (SP) can stimulate secretion of tumor necrosis $factor-\;{\alpha}$ $(TNF-\;{\alpha})$ from astrocytes stimulated with lipopolysaccharide (LPS). Here I report that Sunghyangjungkisan- ga- pogokyoung(Sgp) can modulate cytokines secretion from primary cultures of rat astrocytes. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with LPS and SP. Interleukin-1 (IL-1) has been shown to elevate $TNF-\;{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Treatment of Sgp $(10\;to\;1000\;{\mu}g/ml)$ to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of $TNF-\;{\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Neurodegenerative processes in AD are thought to be driven in part by the deposition of ${\beta}\;-amyloid\;(A\;{\beta})$, a 39- to 43-amino acid peptide product resulting from an alternative cleavage of amyloid precursor protein. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with $A-{\beta}-$and IL-1. These results suggest that Sgp may inhibit $TNF-\;{\alpha}$ secretion by inhibiting IL-1 secretion and that Sgp has an antiinflammatory activity in AD brain

• Journal of Oriental Neuropsychiatry
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• v.18 no.1
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• pp.63-78
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• 2007

Objective : This experiment was designed to investigate the effect of Thalictrum foetidum(TFD) on the Alzheimer's disease. Method : The effects of TFD on amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by amyloid ${\beta}$ $protein(A{\beta})$ and $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA of THP-l cell treated by lipopolysaccharide(LPS), AChE activity of PC-12 cell lysate treated by $A{\beta}$ and behavior of the memory deficit mice induced by scopolamine, and glucose, AChE in serum of the memory deficit mice induced by scopolamine were investigated, respectively. Results : The results were summarized as follows ; 1. TFD suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$. 2. TFD suppressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA in THP-l cell treated by LPS 3.. TFD suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. TFD increased glucose and decreased AChE significantly in the serum of the memory deficit mice induced by scopolamine. 5. TFD group showed significantly inhibitory effect on the scopolamine-induced impairment of learning and memory in the experiment of Morris water maze. Conclusion : According to the above results, it is suggested that TFD might be usefully applied for prevention and treatment of Alzheimer's disease.