• Bulletin of the Korean Chemical Society
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• v.25 no.5
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• pp.601-602
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• 2004

• Molecules and Cells
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• v.40 no.1
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• pp.73-81
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• 2017

The ${\gamma}$-secretase complex represents an evolutionarily conserved family of transmembrane aspartyl proteases that cleave numerous type-I membrane proteins, including the ${\beta}$-amyloid precursor protein (APP) and the receptor Notch. All known rare mutations in APP and the ${\gamma}$-secretase catalytic component, presenilin, which lead to increased amyloid ${\beta}$-peptide production, are responsible for early-onset familial Alzheimer's disease. ${\beta}$-amyloid protein precursor-like (APPL) is the Drosophila ortholog of human APP. Here, we created Notch- and APPL-based Drosophila reporter systems for in vivo monitoring of ${\gamma}$-secretase activity. Ectopic expression of the Notch- and APPL-based chimeric reporters in wings results in vein truncation phenotypes. Reporter-mediated vein truncation phenotypes are enhanced by the Notch gain-of-function allele and suppressed by RNAi-mediated knockdown of presenilin. Furthermore, we find that apoptosis partly contributes to the vein truncation phenotypes of the APPL-based reporter, but not to the vein truncation phenotypes of the Notch-based reporter. Taken together, these results suggest that both in vivo reporter systems provide a powerful genetic tool to identify genes that modulate ${\gamma}$-secretase activity and/or APPL metabolism.

• Journal of Integrative Natural Science
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• v.7 no.2
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• pp.87-91
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• 2014

Amyloid beta ($A{\beta}$) peptide has been implicated in the pathogenesis of Alzheimer's disease and has been reported to induce apoptotic death in cell culture. Cysteine Proteases, a family of enzymes known as caspases, mediate cell death in many models of apoptosis. In the present study, we examined the caspase activity and cell death in $A{\beta}$-treated SHSY5Y cells, as an attempt to elucidate the relationship between the type of caspase and $A{\beta}$-induced cell death. $A{\beta}$ at 20 ${\mu}M$ induce activation of caspase-3, 8 and 9 activity, but not the caspase-1. Caspase-3, 8 and 9 were processed by Ab treatment, consistent with the activity assay. Inhibition of the caspase activities by the selective inhibitors, however, marginally affected the cell death induced by $A{\beta}$. Taken together, the results indicate that $A{\beta}$-induced cell death may be independent of caspase activity and rather, the enzymes might be activated as a result of the cell death.

• Journal of Oriental Neuropsychiatry
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• v.20 no.2
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• pp.31-46
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• 2009

Objectives : This experiment was designed to investigate the effect of Gojineumja(Guzhenyinzi, GJEJ) on damaged neural tissue in cultured glial cells and in the mouse brain tissue. Methods : The effects of the GJEJ on activation of astrocytes and caspase 3-positive cell counts in cultured glial cells administered with ${\beta}$-amyloid peptide were investigated. The effects of the GJEJ on levels of glial fibrillary acidic protein(GFAP)-positive reactive astrocyets and caspase 3-positive cells in the hippocampal subfields in the rats administered with scopolamine were investigated. Results : 1. GJEJ reduced levels of activated astrocytes and caspase 3-positive cell counts in cultured glial cells administered with ${\beta}$-amyloid peptide. 2. GJEJ reduced levels of GFAP-positive reactive astrocyets and caspase 3-positive cells in the hippocampal subfields in the rats administered with scopolamine. Conclusions : The present data. suggest that GJEJ may have a protective function of neuronal and non-neuronal cells in damaged neural tissue caused by AD-like stimulations. Further studies on identification of effective molecular components of GJEJ and their interactions with damaged neural cells would be important for understanding molecular mechanism and may be further applicable for the development of therapeutic strategies.

• 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.

• 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.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.954-960
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• 2004

Expression of the NF-$textsc{k}$B-dependent genes responsible for inflammation, such as TNF-$\alpha$, IL-1$\beta$, and nitric oxide synthase (NOS), contributes to chronic inflammation which is a major cause of neurodegenerative diseases (i.e. Alzheimer＇s disease). Although NF-$textsc{k}$B plays a biphasic role in different cells like neurons and microglia, controlling the activation of NF-$textsc{k}$B is important for its negative feedback in either activation or inactivation. In this study, we found that ursodeoxycholic acid (UDCA) inhibited I$textsc{k}$B$\alpha$ degradation to block expression of the NF-$textsc{k}$B-dependent genes in microglia when activated by $\beta$-amyloid peptide (A$\beta$). We also showed that when microglia is activated by $A\beta$42, the expression of A20 is suppressed. These findings place A20 in the category of ' protective ' genes, protecting cells from pro-inflammatory reper-toires induced in response to inflammatory stimuli in activated microglia via NF-$textsc{k}$B activation. In light of the gene and proteins for NF-$textsc{k}$B-dependent gene and inactivator for NF-$textsc{k}$B (I$textsc{k}$B$\alpha$), the observations now reported suggest that UDCA plays a role in supporting the attenuation of the production of pro-inflammatory cytokines and NO via inactivation of NF-$textsc{k}$B. Moreover, an NF-$textsc{k}$B inhibitor such as A20 can collaborate and at least enhance the anti-inflammatory effect in microglia, thus giving a potent benefit for the treatment of neurodegenerative diseases such as AD.uch as AD.

• Journal of the Korean Applied Science and Technology
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• v.35 no.2
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• pp.389-398
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• 2018

This study was to investigate the antioxidant and anti-amyloid activities of the extract (KP-HE) from Kalopanax pictus (KP) fermented with Hericium erinaceum (HE) mycelium. Antioxidant activity was evaluated based on 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical(ABTS) scavenging assays. In all assays, the extracts from KP, HE and KP-HE had the potential for antioxidant activities. However, antioxidant activity of KP-HE significantly scavenged DPPH radical as compared to the KP and HE. The result suggested that the antioxidant component was increased in the process of KP fermented with HE. KP-HE was shown to significantly inhibite peroxyl radical-mediated DNA strand breakage whereas KP and HE did not inhibit DNA strand breakage. The aggregation of the amyloid-${\beta}$ ($A{\beta}$) peptide is involved in the pathological process of Alzheimer's disease(AD). In this study, the effects of KP, HE and KP-HE on the aggregation of $A{\beta}_{1-42}$ were investigated. KP and HE had little effect on $A{\beta}$ aggregation and KP-HE effectively inhibited $A{\beta}$ aggregation. KP-HE effectively inhibited $A{\beta}$ induced cell death and significantly increased of the 20.3% cell survival at $300{\mu}g/mL$ concentration. KP-HE also decreased intracellular reactive oxygen specie levels in $A{\beta}$-treated cells. The results suggested that KP-HE had antioxidant and anti-amyloid activities. Therefore, KP-HE could potentially be used as a valuable functional food ingredient to prevent neurodegenerative disorders such as AD.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.603-616
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• 2006

The water extract of Gamiyaengshinhwan (GYH), has been used in vitro tests for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with CT105-related dementias and Alzheimer's disease(AD). CT105 derived from proteolytic processing of the $\beta$-amyloid precursor protein (APP), including the amyloid-$\beta$ peptide ($A{\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. We determined that transfected overexpressing APP695 and $A{\beta}$ CT105 have a profound attenuation in the Increase in CT105 expressing neuro2A cells from GYH. Experimental evidence indicates that GYH protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing CT105-associated neuronal degeneration, we demonstrated that GYH inhibits formation of amyloid-$\beta$ fragment ($A{\beta}$ CT105). which are the characteristic, and possibly causative, features of AD. The decreased CT105 $A{\beta}$ in the presence of GYH was observed in the conditioned medium of this CT105-secreting cell line under in vitro. In the cells, GYH significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of Bax, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct CT05 toxicity and the apoptosis initiated by the mitochondria. Multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of CT105 aggregation, underlie the neuroprotective effects of GYH.

• Journal of Ginseng Research
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• v.41 no.4
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• pp.566-571
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• 2017

Background: A number of reports have described the protective effects of ginsenoside Rg1 (Rg1) in Alzheimer's disease (AD). However, the protective mechanisms of Rg1 in AD remain elusive. Methods: To investigate the potential mechanisms of Rg1 in ${\beta}$-amyloid peptide-treated SH-SY5Y cells, a comparative proteomic analysis was performed using stable isotope labeling with amino acids in cell culture combined with nano-LC-MS/MS. Results: We identified a total of 1,149 proteins in three independent experiments. Forty-nine proteins were significantly altered by Rg1 after exposure of the cells to ${\beta}$-amyloid peptides. The protein interaction network analysis showed that these altered proteins were clustered in ribosomal proteins, mitochondria, the actin cytoskeleton, and splicing proteins. Among these proteins, mitochondrial proteins containing HSD17B10, AARS2, TOMM40, VDAC1, COX5A, and NDUFA4 were associated with mitochondrial dysfunction in the pathogenesis of AD. Conclusion: Our results suggest that mitochondrial proteins may be related to the protective mechanisms of Rg1 in AD.