• EDISON SW 활용 경진대회 논문집
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• 제5회(2016년)
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• pp.55-61
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• 2016

$A{\beta}_{40}$ peptides form oligomers that later aggregate into a plaque, which is deemed to be a leading cause of Alzheimer's Disease. Its non-crystalline morphology has limited an understanding of comprehensive structural study. In this research, computational biomolecular simulations were performed in the following order: solvent and ion addition in a box, energy minimization of protein, equilibration, and periodic boundary condition disaggregation of a monomer from fibril. The result founded the two-fold model is 25% more stable in the simulation environment, and the steric zippers held on most tightly until 220 ps of simulation. The study supports the previous findings that two-fold aggregate $A{\beta}_{40}$ is more stable at 310 K and discusses further how much contribution steric-zipper and hydrogen bonding are making.

• 한국식품저장유통학회지
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• 제14권2호
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• pp.213-219
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• 2007

퇴행성 뇌질환의 하나인 알츠하이머는 가벼운 기억력의 장애에서부터 전반적인 인지기능의 장애를 나타내는 질환으로 해마 (hippocampus)를 포함한 신경세포에서 세포사와 관련이 있는 것으로 보고 되어왔다. AP의 자체 독성과 산화 스트레스, $A{\beta}$ plaque에서 나오는 free radical은 세포내 $Ca^{2+}$를 높이고 이로 인해 calpain이 활성화되어 신경 세포사가 촉진되며 microtubule과 같은 cytoskeleton을 파괴시킨다. 이러한 ROS와 $A{\beta}$에 의해 유도되는 세포사멸을 보호하는 물질을 해바라기 씨 추출물을 이용하여 실험을 실시하였다. 우선 추출물이 항산화 효과 (DPPH, FRAP assay), acetylcholinesterase(AChE)의 활성 및 SH-SY5Y cell의 세포사멸에 미치는 영향을 검토하였다. 항산화 활성과 AChE에 대한 억제활성은 해바라기 씨 추출물 처리농도가 높을수록 유의적으로 높게 나타났다. $H_2O_2$와 $A{\beta}$에 의해 유도된 SH-SY5Y에 대한 세포사멸 억제효과 실험(MTT assay)에서 해바라기 씨 추출물이 모두 높은 활성을 나타내었으므로 이의 성분분리는 뇌세포 보호를 위한 좋은 식품재료가 될 수 있다.

• Molecular & Cellular Toxicology
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• 제5권2호
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• pp.108-112
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• 2009

Alzheimer's disease(AD) is a neurodegenerative disorder characterized pathologically by senile plaques, neurofibrillary tangles, and synapse loss. Especially, extracellular beta-amyloid (Abeta) deposition is a major pathological hallmark of Alzheimer's disease (AD). In AD senile plaques, high level of iron and car-bonylated Abeta were detected. Iron has a Lewis acid property which can increase the electrophilicity of carbonyls, which may react catalytically with nucleophiles, such as amines. Hence, this study investigated whether or not iron could promote the carbonylation of amine with malondialdehyde (MDA) in the physiological condition. As the basic study, we examined that iron might promote the conjugation reaction between propylamine, monoamine molecule and MDA in the physiological condition. As the concentration of iron increased, the fluorescence intensity produced from the conjugation reaction increased in a dose-dependent manner. Instead of propylamine, we applied the same reaction condition to Abeta 1-40 peptide, one of major components founded in AD senile plaques for the conjugation reaction. As the result, the fluorescence intensity produced from the conjugation reaction between Abeta 1-40 peptide and MDA showed the similar trend to that of the reaction used with propylamine. This study suggests that iron can accelerate the conjugation reaction of MDA to Abeta 1-40 peptide and play an another important role in deterioration of AD brain.

• 동의생리병리학회지
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• 제17권4호
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• pp.1037-1049
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• 2003

Numerous lines of evidence indicate that some of the neurotoxicity associated with Alzheimer's disease (AD) is due to proteolytic fragments of the amyloid precursor protein (APP). Most research has focused on the amyloid 6 (M). However, the possible role of other cleaved products of APP is less clear. Lately It has been reported that a recombinant carboxy-terminal 105 amino acid fragment (CT105) of APP induced strong nonselective inward currents in Xenopus oocyte. In a brain with Alzheimer's disease (AD), to investigate the roles of carboxyl-terminal fragment (CT105) of amyloid precursor protein (APP) in apoptosis processes possibly linked to neurodegeneration associated with AD, we examined the effects of the CT of APP with 105 amino acid residues (CT105) on the alteration of apoptosis triggers in neubroblastoma cells. We have investigated whether Radix Polygalae and Rhizoma Acori Graminei mixture extract (RP+RAG) inhibits CT105-induced apoptosis of neuroblastoma cells. We found that RP+RAG inhibits CT105-induced apoptosis in SK-N-SH cells. Treatment of the cells with RP+RAG inhibited CT105-induced DNA fragmentation and Tunel assay of nuclear chromatin and inhibited the caspase-3 expression in SK-N-SH cells. As the result of this study, In RP+RAG group, the apoptosis in the nervous system is inhibited, the repair against the degerneration of neuroblastoma cells by CT105 expression is promoted. These results indicate that RP+RAG possess strong inhibitory effect of apoptosis in the nervous system and repair effect against the degeneration of neuroblastoma cells by CT105 expression

• Journal of Ginseng Research
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• 제42권4호
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• pp.401-411
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• 2018

Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid ${\beta}$-protein ($A{\beta}$) formation by inhibiting ${\beta}$- and ${\gamma}$-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and $A{\beta}$-induced neurotoxicity, and decrease $A{\beta}$-induced production of reactive oxygen species and neuro-inflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates $A{\beta}$-induced cholinergic deficits in AD models. Similarly, gintonin inhibits $A{\beta}$-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce $A{\beta}$ formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.

• 대한한의학회지
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• 제30권3호
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• pp.1-14
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• 2009

Objectives : Alzheimer's disease (AD) is characterized by neuronal loss and extracellular senile plaque. Moreover, the cellular actions of ${\beta}$-amyloid (A${\beta}$ play a causative role in the pathogenesis of AD. This study was designed to determine whether Woo-Gui-Um, a commonly used Korean herbal medicine, has the ability to protect cortical and hippocampal neurons against A${\beta}_{25-35}$ neurotoxicity Methods : In the present study, the authors investigated the preventative effects of the water extract of Woo-Gui-Um in a mouse model of AD. Memory impairment was induced by intraventricularly (i.c.v.) injecting A${\beta}_{25-35}$ peptides into mice. Woo-Gui-Um extract was then administered orally (p.o.) for 14 days. In addition, A${\beta}_{25-35}$ toxicity on the hippocampus was assessed immunohistochemically, by staining for Tau, MAP2, TUNEL, and Bax, and by performing an in vitro study in PC12 cells. Results : Woo-Gui-Um extract had an effect to improve learning ability and memory score in the water maze task. Woo-Gui-Um extract had significant neuroprotective effects in vivo against oxidative damage and apoptotic cell death of hippocampal neurons caused by i.c.v. A${\beta}_{25-35}$. In addition, Woo-Gui-Um extract was found to have a protective effect on A${\beta}_{25-35}$-induced apoptosis, and to promote neurite outgrowth of nerve growth factor (NGF)-differentiated PC12 cells. Conclusions : These results suggest that Woo-Gui-Um extract reduces memory impairment and Alzheimer's dementia via an anti-apoptotic effect and by regulating Tau and MAP2 in the hippocampus.

• Nuclear Medicine and Molecular Imaging
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• 제41권3호
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• pp.241-246
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• 2007

목적: 베타아밀66로이드 양전자단층촬영 영상 추적자인 $[^{11}C]OH-BTA-1(1)$는 알쯔하이머병의 진단용으로 개발되었다. 반응용매 루프 방법에 의한 $[^{11}C]1$는 $[^{11}C]MeOTf$를 통해서 한번의 반응으로 $^{11}C$을 바로 표지 할 수 있다. 또한 반응 중에 $[^{11}C]2$가 생긴다는 것이 보고된바 있다. 하지만, 실험 중에 다른 부산물이 생기는 것이 발견되어 그 물질을 추정하고, 각 반응용매에 따른 $[^{11}C]1$과 부산물의 표지효율 변화에 대한 조사를 했다. 대상 및 방법: 사이클로트론에서 $^{14}N(p,{\alpha})^{11}C$ 핵반응과 미량의 $O_2$로 부터 의하여 생산되는 $[^{11}C]CO_2$를 0.2 M $LiAlH_4/THF$ 0.2 ml로 환원한 다음 HI 1ml과 반응하여 $[^{11}C]CH_3I$를 생산했다. 질소가스를 20 ml/min로 불어 주면서 200C 에서 AgOTf-Graphpac GC column를 통과시켜 $[^{11}C]CH_3OTf$를 생산했다. 각 반응용매 (MEK, CHO, DEK, DMF) 100 1에 녹인 전구물질 1 mg를 고성능 액체 크로마토그래피 시료 루프에 미리 주입하고 $[^{11}C]CH_3OTf$를 상온에서 7분 동안 질소가스를 불어줬다. Semi-preparative HPLC로 분리하였다. 결과: 각 반응용매에서 $[^{11}C]1$에 표지효율은 MEK: $86.0{\pm}5.5%$, CHO: $59.7{\pm}2.4%$, DEK: $29.9{\pm}1.8%$, DMF: $7.6{\pm}0.5%$이었다. MEK에서 얻은 $[^{11}C]1$의 비방사능은 98 ($GBq/{\mu}mol$)이다. 각 물질의 질량 분석은 1: m/z 257.3 (M+1), 2: 257.3 (M+1), 3: 271.3 (M+1)이었다. 각 생성물질의 표지효율은 MEK에서 $86.0{\pm}5.5%:5.0{\pm}3.4%:1.5{\pm}1.3%$ $([^{11}C]1:[^{11}C]2:[^{11}C]3)$, CHO에서 $59.7{\pm}2.4%:4.7{\pm}3.2%:1.3{\pm}0.5%$, DEK에서 $29.9{\pm}1.8%:2.0{\pm}0.7%:0.3{\pm}0.1%$, DMF에서 $7.6{\pm}0.5%:0.0%:0.0%$이다. 결론: $[^{11}C]1$은 4가지 반응용매 중 MEK 반응용매에서 가장 높은 표지효율을 나타냈다. 부산물인 $[^{11}C]3$은 고성능 액체 크로마토그래피의 자외선, 방사능 검출기와 질량 분석법을 통해 물질을 추정할 수 있었다.

• 핵의학기술
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• 제20권2호
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• pp.42-45
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• 2016

$^{18}F-Florbetaben$은 베타아밀로이드 병리를 확인하여 인지 장애 및 의심 환자에게 보조적 진단으로 사용되고 있다. 지질 친화성의 특성과 에탄올이 첨가된 약제의 특성상 주사 후 3-way Set에 잔량과 주사 시 환자의 통증이 관심의 대상이 된다. 본 연구는 효과적인 방사성의약품의 주사와 환자 케어 및 우수한 영상을 위함이다. 내원환자 70명을 대상으로 하였고, 환자들에게 평균 $259{\pm}74MBq$의 $^{18}F-FDG$ (20명), $^{18}F-FP-CIT$ (20명), $^{18}F-Florbetaben$ (30명)을 3-way Set으로 주사(Reflusing 2회, Reflusing 3회 이상)를 하여 주사 후 잔량을 측정하였고, $^{18}F-Florbetaben$ 주사 시 사용되는 3-way Set와 Heparin Cap의 효율적인 주사방법을 알아보기 위해서 주사 후 잔량을 측정하여 SPSS 12.0 ANOVA, t-test 통계분석을 통하여 잔량을 비교분석 하였다. 그리고 $^{18}F-Florbetaben$의 통증 유발 성분의 에탄올 양을 측정하기 위하여 Gas Chromatography로 추가 분석을 실시해보았다. Reflusing 2회 시 $^{18}F-FDG$: 1.48 MBq (0.04 mCi), $^{18}F-FP-CIT$: 7.4 MBq (0.2 mCi), $^{18}F-Florbetaben$: 32.6 MBq (0.88 mCi)의 잔량이 측정 되었고 Reflusing 3회 이상 시 $^{18}F-FDG$: 1.85 MBq (0.05 mCi), $^{18}F-FP-CIT$: 3.7 MBq (0.10 mCi), $^{18}F-Florbetaben$: 36.3 MBq(0.98 mCi)의 잔량이 측정 되었다. 다중 비교결과 Reflusing 2회 시 잔량이 유의미한 차이가 있었고(P < 0.05), 3회 이상 시 $^{18}F-Florbetaben$과 $^{18}F-FDG$, $^{18}F-FP-CIT$는 잔량의 유의미한 차이가 있었으며(P < 0.05), $^{18}F-FDG$와 $^{18}F-FP-CIT$는 유의미한 차이가 없었다(P > 0.05). $^{18}F-Florbetaben$ 주사 후 잔량은 3-way Set: 32.6 MBq (0.88 mCi), 36.3 MBq (0.98 mCi)였고 Heparin Cap: 7.03 MBq (0.19 mCi)으로 유의미한 차이가 있었다(P < 0.05). Gas Chromatography 분석결과 에탄올: 207665 ppm, 아세톤: 377.4 ppm으로 나타났다. $^{18}F-Florbetaben$은 $^{18}F-FDG$와 $^{18}F-FP-CIT$에 비해 주사 후 잔량이 많았고, 통증을 유발하는 에탄올 성분의 수치가 높게 나타났다. 주사 시 3-way Set 방식보다는 Heparin Cap을 사용함이 잔량 감소에 더 효과적이었다. 그리고 주사 시 환자의 통증 완화를 위해서 천천히 주사함을 권고한다.