• 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 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.

• 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.

• 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.

• 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 Plant Biotechnology
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• v.47 no.4
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• pp.283-288
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• 2020

Although the evolution of Arabidopsis thaliana and humans diverged approximately 1.6 billion years ago, recent studies have demonstrated that protein function and cellular processes involved in disease response remain remarkably conserved. Particularly, γ-secretase, a multisubunit protein complex that participates in intramembrane proteolysis (RIP) regulation, is also known to mediate the cleavage of more than 80 substrates including the amyloid precursor protein (APP) and the Notch receptor. Although the genes (PS1/2, APH-1, PEN-2, and NCT) coding for the γ-secretase complex components are present in plant genomes, their function remains largely uncharacterized. Given that the deposition of 42 amino acid long amyloid-β peptides (hAβ₄₂) is thought to be one of the main causes of Alzheimer's disease, we aimed to examine the physiological effects of hAβ₄₂ peptides on plants. Interestingly, we found that Arabidopsis protoplast death increased after 24 h of exposure to 3 or 5 µM hAβ₄₂ peptides. Furthermore, transgenic Arabidopsis plants overexpressing the hAβ₄₂ gene exhibited changes in primary root length and silique phyllotaxy. Taken together, our results demonstrate that hAβ₄₂ peptides, a metazoan protein, significantly affect Arabidopsis protoplast viability and plant morphology.

• Journal of Oriental Neuropsychiatry
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• v.18 no.2
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• pp.101-132
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• 2007

Objective : This research investigates the effect of the NogYongDaeBoTang,(NYDBT) on Alzheimer's disease. Method : The effects of the NYDBT extract on (1) $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) acetylcholinesterase(AChE), amyloid precursor proteins(APP), and glial fibrillary acidic protein(GFAP) mRNA the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, $IL-1{\beta}$ mRNA, and $TNF-{\alpha}$ mRNA; (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer‘s diseased mice induced with ${\beta}A$ were investigated. Results : 1. The NYDBT extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in BV2 microglia cell line treated with LPS. 2. The NYDBT extract suppressed the expression of $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ protein production in BV2 microglia cell line treated with LPS. 3. For the NYDBT extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by $A{\beta}$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 4. The NYDBT extract suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, and CD68/CD11b, in the mice with Alzheimer's disease induced by $A{\beta}$. 5. The NYDBT extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by $A{\beta}$. 6. The NYDBT extract reduced the Tau protein, GFAP protein, and presenilin1/2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by $A{\beta}$. Conclusions : These results suggest that the NYDBT extract may be effective for the prevention and treatment of Alzheimer's disease.

• Journal of Oriental Neuropsychiatry
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• v.13 no.1
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• pp.79-115
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• 2002

This research investigates the effect of the Crataegus pinnatifida BGE. var. major N.E. BR(CPVM) on Alzheimer's disease. Specifically, the effects of the DYHT extract on (1) $IL-1{\beta}$, IL-6, amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA of PC-12 cells treated with CTI05; (2) the AChE activity and the APP production of PC-12 cell treated with CT105; (3) the behavior; and (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, reactive oxygen species(ROS), nitrite oxide(NO); and (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with CT105 were investigated. The results are as follow. 1. The CPVM extract suppressed the expression of $IL-1{\beta}$, IL-6, APP, AChE, and GFAP mRNA in PC-12 cells treated with CT105. 2. The CPVM extract suppressed the AChE activity and the production of APP significantly in PC-12 cells treated with CT105. 3. The CPVM extract group showed a significant inhibitory effect on the memory deficit for the mice with Alzheimer's disease induced by CT105 in the Morris water maze experiment. 4. The CPVM extract suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, ROS and NO in the mice with Alzheimer's disease induced by CT105. 5. The CPVM extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by CT105. These results suggest that the CPVM extract may be effective for the prevention and treatment of Alzheimer's disease.

• Environmental Mutagens and Carcinogens
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• v.25 no.1
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• pp.19-24
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• 2005

The Swedish double mutation (KM670/671NL) of amyloid precursor protein (Swe-APP) is associated with early-onset familial Alzheimer's disease (FAD) and increases amyloid beta peptide production. Although APP/A/3 mediated neurotoxicity is observed both in vitro and in vivo, the relationship between mutant APP expression, A/3 production, and neuronal death observed in the brains of FAD patients remains to be elucidated. In this study, we investigated the mechanisms of Swe-APP-induced cell death in HEK293 and NGF-differentiated PC 12 cells. We found that the expression of Swe-APP induced cytochrome C relase, activation of caspase 3 in HEK 293 and NGF-differentiated PC 12 cells. We also show that the reactive oxygen species (ROS) was detected in Swe-APP expressing HEK 293 cells and NGF-differentiated PC 12 cells and that pretreatment with vitamine E attenuated the cellular death, cytochrome C release induced by Swe-APP expression, indicating the involvement of free radical in these processes. These results suggest one of possible apoptotic mechanisms of Swe-APP which could occur through cytochrome C release from mitochondria and this apoptosis inducing effects could be at least in part, due to ROS generation by Swe-APP expression.

• Journal of Haehwa Medicine
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• v.8 no.1
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• pp.793-825
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• 1999

For the development of drugs for alzheimer,s disease, the study was done to review the oriental pathology, clinical data, recent trends for research and strategy for future study. The results were as follows: 1. The medical term Chi-dsi implying alzheimer,s disease was referred for the first time in a medical book, Hwatasheneubijeon written by Hwa-Ta and its differentiation and treatment were studied more in Ming or Ching dynasties. Chi-dai can be differentated as weak(虛) syndrome and Shi(實) syndrome. This can be caused by deficiencies of renal Yin, renal Yang, cardiac Yin and hepatic blood, while that by deficiencies of pathological fluid(痰飮) and clotted blood(瘀血). 2. Dementia can be roughly classified as alzheimer's disease and multi-infarct disease. Its causes were known to be cholinergic transmitter, C-peptide, amyloid-${\beta}$, apolipoprotein, APP(amyloid precursor protein), TGF, MMP-9 and free radical. 3. In Korea experimental studies were chiefly done for the elimataion of C-peptide, amyloid-${\beta}$, apolipoprotein, APP for alzheimer's disease, for the development of drug inhibiting degerative change following CVA and loss of memory and also administrative measure was done by support of government. 4. Drugs of dimentia developed so far were Chi-Dai dan, extracts from aloe, mushroom, green tea, Ganoderma and also folic acid, vitamin C, DHEA and silk amino acid were reported to be effective in dimenta. 5. Future strategic research had better be done on dementia-inducing factors such as acetylcholine, C-peptide, amyloid-${\beta}$, apolipoprotein, APP, TGF, MMP-9 and free radical, development of animal model for dimentia, clinical study, epidemiology, nursing and administrative studies and also consortium for dimentia research should be formed so that repeated investment be avoided.