• Molecules and Cells
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• v.42 no.1
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• pp.36-44
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• 2019

Alzheimer's disease (AD) is the most frequent age-related human neurological disorder. The characteristics of AD include senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. ${\beta}-Amyloid$ ($A{\beta}$) peptide is the predominant proteinaceous component of senile plaques. The amyloid hypothesis states that $A{\beta}$ initiates the cascade of events that result in AD. Amyloid precursor protein (APP) processing plays an important role in $A{\beta}$ production, which initiates synaptic and neuronal damage. ${\delta}-Catenin$ is known to be bound to presenilin-1 (PS-1), which is the main component of the ${\gamma}-secretase$ complex that regulates APP cleavage. Because PS-1 interacts with both APP and ${\delta}-catenin$, it is worth studying their interactive mechanism and/or effects on each other. Our immunoprecipitation data showed that there was no physical association between ${\delta}-catenin$ and APP. However, we observed that ${\delta}-catenin$ could reduce the binding between PS-1 and APP, thus decreasing the PS-1 mediated APP processing activity. Furthermore, ${\delta}-catenin$ reduced PS-1-mediated stabilization of APP. The results suggest that ${\delta}-catenin$ can influence the APP processing and its level by interacting with PS-1, which may eventually play a protective role in the degeneration of an Alzheimer's disease patient.

• Proceedings of the KOSOMBE Conference
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• v.1997 no.11
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• pp.475-477
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• 1997

We have analyzed the fluorescence image obtaining from green fluorescence protein (GFP). In order to monitor the fluorescence of specific gene, we used the amyloid precursor protein promoter which has been known to act as a major role in the development of Alzheimer's disease. The promoter from - 3.0 kb to + 100 base pair was inserted into the gene expression monitoring GFP vector purchased from Clontech. This construct was transfected into the PC 12 and fibroblast cells and the fluorescence image was captured by two kinds of methods. One is using cheaper CCD camera and other is SIT-CCD camera. or the higher sensitivity of the fluorescence image, we developed the multiple image grabbing program. As a results, the fluorescence image by conventional CCD camera have the similar sensitivity compared with that of the SIT-camera by applying the multiple image grabbing programs. By this system. it will be possible to construct the fluorescence monitoring system with lower cost. And gene expression in real time by fluorescence image will be possible without changing the fluorescence images.

• Journal of Oriental Neuropsychiatry
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• v.17 no.2
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• pp.75-89
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• 2006

Objective : This experiment was designed to investigate the effect of Rhododendron simsii Planch(RSP) on the Alzheimer's disease. Method : The effects of RSP 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-1 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. Result : 1. RSP suppressed APP, AChE, GFAP mRNA in PC-12 celt treated by $A{\beta}$. 2. RSP suppressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA in THP-1 cell treated by LPS. 3. RSP suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. RSP increased glucose and decreased AChE significantly in the serum of the memory deficit mice induced by scopolamine. 5. RSP group showed significantly inhibitory effect on the scopolamine-induced impairment of teaming and. memory in the experiment of Morris water maze. Conclusion : According to the above results, it is suggested that RSP might be usefully applied for prevention and treatment of Alzheimer's disease and memory deficit symptom.

• Journal of Oriental Neuropsychiatry
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• v.20 no.1
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• pp.235-247
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• 2009

Objectives : Ginseng Radix Rubra water extract(RGE) has been used in vivo test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease (AD). APP 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. Methods : We determined that RGE inhibits formation of APP, which are the behavior, and possibly causative, feature of AD. Results and Conclusions : In the cells, RGE significantly activated antiapoptosis and decreased the activity of APP-grim, 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 APP toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of APP, underlie the neuroprotective effects of RGE.

• Journal of Oriental Neuropsychiatry
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• v.20 no.2
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• pp.121-131
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• 2009

Objectives : From Scrophularia buergeriana water extract(SBW), has been used in vivo test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease(AD). $A{\beta}$ oligomer derived from proteolytic processing of the ${\beta}$-amyloid precursor protein(APP), including the amyloid-${\beta}$ peptide($A{\beta}$), play a critical role in the pathogenesis of Alzheimer's dementia. Methods : Using drosophila APP model on APP-induced neuronal cytotoxicity, we demonstrated that SBW prevents neurotoxicity of $A{\beta}$ oligomer, which are the behavior, and possibly causative, feature of AD. We investigated the neuroprotective effects of SBW against the effects of oligomeric $A{\beta}$ and fly behaveior and life span by UAS-GRIM/APP-GAL within transgenic flies. Results and Conclusions : SBW repaired damage leading to the behaveior of APP-induced fly and delayed life span. These results suggest that neuronal damage in AD might be due to two factors: a direct $A{\beta}$ oligomer toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of $A{\beta}$ oligomer, underlie the neuroprotective effects of SBW.

• Korean Journal of Medicinal Crop Science
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• v.28 no.2
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• pp.85-94
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• 2020

Background: Alzheimer's disease (AD) is caused by various factors, such as cholinergic dysfunction, regulation of neurotrophic factor expression, and accumulation of amyloid-beta. We investigated whether or not a combination of Carthamus tinctorius L. seed and Taraxacum coreanum (CT) has a protective effect on scopolamine-induced memory impairment in a mouse model. Methods and Results: Mice were orally pretreated with CT (50, 100 and 200 mg/kg/day) for 14 days, and scopolamine (1 mg/kg/day) was injected intraperitoneally before subjecting them to behavior tests. CT-administered mice showed better novel object recognition and working memory ability than scopolamine-treated control mice. In T-maze and Morris water maze tests, CT (100 and 200 mg/kg/day) significantly increased space perceptive ability and occupancy to the target quadrant, respectively. In addition, 100 and 200 mg/kg/day of CT attenuated cholinergic dysfunction through inhibition of butyryl cholinesterase in brain tissue. Furthermore, CT-administered mice showed higher cyclic adenosine monophosphate-response element-binding protein (CREB) levels and lower amyloid precursor protein (APP) levels compared to scopolamine-treated control mice. Conclusions: CT improved scopolamine-induced memory impairment through inhibition of cholinergic dysfunction, up-regulation of CREB, and down-regulation of APP. Therefore, CT could be a useful therapeutic agent for AD with protective effects on cognitive impairment.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.3
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• pp.189-195
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• 2013

Amyloid-${\beta}$ peptide ($A{\beta}$), generated by proteolytic cleavage of the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). The key step in the generation of $A{\beta}$ is cleavage of APP by beta-site APP-cleaving enzyme 1 (BACE1). Levels of BACE1 are increased in vulnerable regions of the AD brain, but the underlying mechanism is unknown. In the present study, we reported the effects of ferrous ions at subtoxic concentrations on the mRNA levels of BACE1 and a-disintegrin-and-metalloproteinase 10 (ADAM10) in PC12 cells and the cell responses to ferrous ions. The cell survival in PC12 cells significantly decreased with 0 to 0.3 mM $FeCl_2$, with 0.6 mM $FeCl_2$ treatment resulting in significant reductions by about 75%. 4,6-diamidino-2-phenylindole (DAPI) staining showed that the nuclei appeared fragmented in 0.2 and 0.3 mM $FeCl_2$. APP-${\alpha}$-carboxyl terminal fragment (APP-${\alpha}$-CTF) associations with ADAM10 and APP-${\beta}$-CTF with BACE1 were increased. Levels of ADAM10 and BACE1 mRNA increased in response to the concentrations of 0.25 mM, respectively. In addition, p-ERK and p-Bad (S112, S155) expressions were increased, suggesting that APP-CTF formation is related to ADAM10/ BACE1 expression. Levels of Bcl-2 protein were increased, but significant changes were not observed in the expression of Bax. These data suggest that ion-induced enhanced expression of AMDA10/BACE1 could be one of the causes for APP-${\alpha}/{\beta}$-CTF activation.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.33-46
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• 2006

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disease associated with aging in the human population. This disease is characterized by the extracellular deposition of beta-amyloid peptide $(A{\beta})$ in cerebral plaques. $A{\beta}$ is derived from the ${\beta}-amyloid$ precursor protein (APP) by the enzymes, ${\beta}-$ and ${\eta}o-secretase$. Compounds that ${\beta}-$ or ${\eta}o-secretase$ inhibit activity, can reduce the production of $A{\beta}$ peptides, and thus have therapeutic potential in the treatment of AD. Increasing body of evidence has been demonstrated that Bee Venom(BV) Acupuncture could compete with complex protein involving in multiple step of $NF-{\kappa}B$ activation and exert the anti-inflammatory potential of combined inhibition of the prostanoid and nitric oxide synthesis systems by inhibition of IKK and $NF-{\kappa}B$. In this study, I investigated possible effects of BV on memory dysfunction caused by lipopolysaccharide (LPS) and $A{\beta}$ through inhibition of secretases activities and $A{\beta}$ aggregation. I examined the improving effect of BV on the LPS (2.5 mg/Kg, i.p.)-induced memory dysfunction using passive avoidance response and water maze tests in the mice. BV (0.84, $1.67\;{\mu}g/ml$) reversed the LPS-induced memorial dysfunction in dose dependent manner. BV also dose-dependently attenuated LPS-induced ${\beta}$ and ${\eta}o-secretase$ activities in cerebral cortex and hippocampus of the mice brain. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.43-51
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• 2006

This experiment was designed to investigate the effect of Amomum villosum(AMV) on the Alzheimer's disease. The effects of AMV extract on amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell line treated by amyloid $\beta$ protein($A{\beta}$) : IL-$1{\beta}$, IL-6, TNF-$\alpha$ mRNA of THP-1 cell line treated by lipopolysaccharide(LPS) : AChE activity of PC-12 cell lysate treated by $A{\beta}$ : serum glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine : behavior of memory deficit mice induced by scopolamine were investigated, respectively. AMV extract suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$ : IL-$1{\beta}$, IL-6, TNF-$\alpha$ mRNA in THP-1 cell treated by LPS , AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. AMV extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. AMV extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that AMV extract might be usefully applied for prevention and treatment of Alzheimer's disease.

• Bulletin of the Korean Chemical Society
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• v.27 no.9
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• pp.1371-1376
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• 2006

BACE 1 ($\beta$-secretase), a membrane bound aspartic protease, is a key enzyme in the process of amyloid precursor protein (APP) into A$\beta$ peptide which is considered to play a causative role in Alzheimers Disease (AD). Here, we reported the synthesis and inhibitory activity of optically active 3-amino-4-aryl-piperidines.