• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.172.2-172.2
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• 2000

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2011년도 추계학술발표회
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• pp.31-45
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• 2011

The amyloid ${\beta}$-peptide ($A{\beta}$), which originates from the proteolytic cleavage of amyloid precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease (AD). Mounting evidence indicates that different species of $A{\beta}$, such as $A{\beta}$ oligomers and fibrils, may contribute to AD pathogenesis via distinct mechanisms at different stages of the disease. Importantly, elevation and accumulation of soluble $A{\beta}$ oligomers closely correlate with cognitive decline and/or disease progression in animal models of AD. In agreement with these studies, oligomers of $A{\beta}$ have been shown to directly affect synaptic plasticity, a neuronal process that is known to be essential for memory formation. Our previous studies showed that $A{\beta}$ induces the breakdown of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a phospholipid that regulates key aspects of neuronal function. PI(4,5)P2 breakdown was found to be a key step toward synaptic and memory dysfunction in a mouse model of AD. To this end, we seek to identify small molecules that could elevate the levels of PI(4,5)P2 and subsequently block $A{\beta}$ oligomer-induced breakdown of PI(4,5)P2 and synaptic dysfunction.. We found that (20S)Rg3, an active triterpene glycoside from heat-processed ginseng, serves as an agonist for phosphatidylinositol 4-kinase IIalpha (PI4KIIalpha), which is a lipid kinase that mediates a rate-limiting step in PI(4,5)P2 synthesis. Consequently, (20S)Rg3 stimulates PI(4,5)P2 synthesis by directly stimulating the activity of PI4KIIalpha. Interestingly, treatment of a mouse model of AD with (20S)Rg3 leads to reversal of memory deficits. Our data suggest that the PI(4,5)P2-promoting effects of (20S)Rg3 may help mitigate the cognitive symptoms associated with AD.

• 동의신경정신과학회지
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• 제20권2호
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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.

• 동의생리병리학회지
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• 제20권1호
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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.

• 대한본초학회지
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• 제29권6호
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• pp.73-83
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• 2014

Objectives : This study was investigated the effects of the root of Polygala tenuifolia (POL) on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Methods : Chronic cerebral hypoperfusion was produced by permanent bilateral common carotid artery occlusion (pBCAO). POL was administered orally once a day (130 mg/kg of water-extract) for 28 days starting at 4 weeks after the pBCAO. The acquisition of learning and the retention of memory were tested on 9th week after the pBCAO using the Morris water maze. In addition, effects of POL on $A{\beta}$ generation and expressions of APP and BACE1 were observed in the hippocampus of rats. Results : POL significantly prolonged the swimming time spent in target quadrant and significantly reduced the swimming time spent in the quadrant far from the target. POL significantly increased the percentage of swim in the targer quadrant in the retention test, while POL was not effective on the escape latencies in the acquisition training trials. POL significantly reduced the levels of $A{\beta}_{(1-40)}$ and $A{\beta}_{(1-42)}$ in the cerebral cortex and the level of $A{\beta}_{(1-42)}$ in the hippocampus produced by chronic cerebral hypoperfusion. POL also significantly attenuated the up-regulation of APP and BACE1 expression in the hippocampus produced by chronic cerebral hypoperfusion. Conclusions : The results show that POL alleviated memory deficit and up-regulation of $A{\beta}$ and BACE1 expressions in the hippocampus. This result suggests that POL may exert ameliorating effect on memory deficit through inhibition of ${\beta}$-secretase activity and $A{\beta}$ generation.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.203.2-204
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• 2003

As medicinal knowledge developed. population system has been migrating into the aged society. These aged society evokes the social problem of senile diseases. One of these. Alzheimer's Disease (AD) has been an issue. and its causative. ${\beta}$-amyloid(A${\beta}$) has also been a key target in drug development. In AD, microglial cell affects neuron cells in any way of positive and negative. (omitted)

• 동의신경정신과학회지
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• 제20권2호
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• pp.1-17
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• 2009

Objectives : Alzheimer's disease(AD) is the most common form of dementia, which is characterized by progressive deterioration of memory and higher cortical functions that ultimately results in total degradation of intellectual and mental activities. Nokyongdaebo-tang(Lurongdabutang) has been usually used for the treatment for the deficiency syndrome dementia and amnesia. This experiment was designed to investigate the effect of the Nokyongdaebo-tang(Lurongdabutang) hot water extract on pathological AD model. Methods : The effects of the Nokyongdaebo-tang(Lurongdabutang) hot water extract on cultured spinal cord cells induced by ${\beta}$-amyloid were investigated. The effects of the Nokyongdaebo-tan(Lurongdabutang) hot water extract on the memory deficit mice induced by scopolamine were investigated. Results : 1. ${\beta}$-amyloid treatment on cultured spinal cord cells increased both GFAP-staining intensity of astrocytes and caspase 3 immunoreactivity on cultured cells. Then, Nokyongdaebo-tang(Lurongdabutang) treatment reduced the labeling intensity for both GFAP and caspase 3 proteins in culture cells. 2. Scopolamine treatment into mice increased levels of GFAP-positive astrocytes and caspase 3-labeled cells of the hippocampal subfields dentate hilar region, CA3 and CA1 area. In vivo administration of Nokyongdaebo-tang(Lurongdabutang) attenuated labeling intensity for those two proteins in the same hippocampal areas. Similar effects were observed by the treatment of galanthamine, an inhibitor of acetylcholinesterase. Conclusions : This experiment shows that the Nokyongdaebo-tang(Lurongdabutang) may play a protective role in damaged neural tissues. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. Nokyongdaebo-tang(Lurongdabutang) might be effective for the prevention and treatment of AD.

• 동의생리병리학회지
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• 제22권5호
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• pp.1215-1222
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• 2008

Recent studies indicate that the deposition of ${\beta}$-amyloid ($A{\beta}$) is associated with the pathogenesis of Alzheimer's disease (AD), but the underlying mechanism is not clear yet. To investigate the effects of Jangwonhwangagambang (JWHG) extract on AD pathogenicity, we have generated transgenic Drosophila model in which GMR-APP-GAL4/UAS-GRIM system was designed to overexpress amyloid precursor protein(APP), We examined fly's survival ratio, flight behavior, and morphological patterns of chest and eye. We found that JWHG treatment improved fly's survival ratio by inhibiting apoptosis and flight behavior. APP-GRIM transgenic flies treated with JWHG showed had significantly lower levels of APP deposition in the chest and eye compared to control animals. JWHG treatment further inhibited chest and eye degeneration. These results suggest that JWHG prevents APP-induced neurotoxicity, and thus may be applicable for the development of preventive or therapeutic agents for AD treatment.

• 동국한의학연구소논문집
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• 제8권1호
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• pp.171-190
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• 1999

본 실험은 전갈 추출물이 어혈병태 모델과 KCN으로 유발된 전뇌허혈, 뇌세포독성 등에 미치는 영향을 관찰하였다. 전갈은 Dextran에 의해 유도된 혈전으로 감소된 혈소판수, fibrinogen량, hemocrit치를 유의성 있게 증가시키고, 증가된 prothrombin time을 유의성 있게 단축시켰다. 전갈은 thrombin과 ADP에 의해 유도된 혈소판 응집을 억제하였으나 collagen에 의해 유도된 혈소판 응집에는 저해효과를 나타내지 않았다. 또한 collagen과 epinephrine에 의해 유도된 pulmonary embolism에 대하여 보호 효과를 나타내었다. 전갈은 KCN에 의한 전뇌허혈 유발 실험에서 혼수시간을 유의성 있게 단축시켰고, Amyloid ${\beta}$ protein(25-35)에 의해 유도된 PC12 세포의 독성에 대하여 보호효과를 나타내었다.

• 생명과학회지
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• 제29권6호
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• pp.740-746
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• 2019

운동은 치매에 긍정적인 영향을 줄 수 있다고 잘 알려져 있다. 그러나 대부분의 치매 관련 연구에서는 치매의 증상 완화, 치매에 관한 다양한 치료 및 약물 치료에 대한 연구가 대부분이었다. 규칙적인 운동은 뇌 기능과 치매예방에 중요한 역할을 하지만, 치매와 뇌 기능에 대한 운동의 효과를 나타내는 연구는 부족한 실정이다. 본 연구에서는 운동이 수면 관련 인자(melatonin, serotonin), 치매 관련 인자(BDNF, beta-amyloid, IGF-1, Irisin, GLUT)에 미치는 영향에 대해 연구하고자 한다. 본 연구는 Myokine (Irisin, IGF-1), GLUT 및 Melatonin이 지구성 운동을 통한 BDNF 활성화를 통해 치매 증상을 개선하거나 지연시키는 중요한 인자라는 것을 밝혀냈다. 그러나 이러한 결과는 다양한 종류의 운동 유형, 형태, 기간 및 운동 강도 등에 따라 다른 결과가 나타나서 논란의 여지가 있다. 그러므로 추후 운동과 치매에 관한 기전적인 연구분석이 필요하다.