• 제목/요약/키워드: ${\beta}$-secretase

검색결과 65건 처리시간 0.022초

Mercury induced the Accumulation of Amyloid Beta (Aβ) in PC12 Cells: The Role of Production and Degradation of Aβ

  • Song, Ji-Won;Choi, Byung-Sun
    • Toxicological Research
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    • 제29권4호
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    • pp.235-240
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    • 2013
  • Extracellular accumulation of amyloid beta protein ($A{\beta}$) plays a central role in Alzheimer's disease (AD). Some metals, such as copper, lead, and aluminum can affect the $A{\beta}$ accumulation in the brain. However, the effect of mercury on $A{\beta}$ accumulation in the brain is not clear. Thus, this study was proposed to estimate whether mercury concentration affects $A{\beta}$ accumulation in PC12 cells. We treated 10, 100, and 1000 nM $HgCl_2$ (Hg) or $CH_3HgCl_2$ (MeHg) for 48 hr in PC12 cells. After treatment, $A{\beta}_{40}$ in culture medium increased in a dose- and time-dependent manner. Hg and MeHg increased amyloid precursor protein (APP), which is related to $A{\beta}$ production. Neprilysin (NEP) levels in PC12 cells were decreased by Hg and MeHg treatment. These results suggested that Hg induced $A{\beta}$ accumulation through APP overproduction and reduction of NEP.

강원도 10종 산채류의 항산화 및 인지능력개선 효능 평가 (Evaluation of Antioxidant and Cognition Improvement Effects of 10 Wild Vegetables Cultivated in Gangwon Province)

  • 한웅호;최선일;김민종;이옥환
    • 한국식품영양학회지
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    • 제32권6호
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    • pp.662-668
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    • 2019
  • The purpose of this study was to investigate effect of methanolic extracts of 10 kinds of wild vegetables cultivated in Gangwon province on antioxidant activity, acetylcholinesterase, and β-secretase inhibitory activities. Results showed that among the wild vegetables, Aralia elata(Miq.) Seem shoot extract exhibited the highest total phenol content (84.65±1.08 mg GAE/g) and total flavonoids content (70.77±0.55 mg RE/g), respectively. The antioxidant activity of wild vegetables extracts was measured by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. Aralia elata(Miq.) Seem shoot extracts had the highest DPPH and ABTS scavenging activity (90.16%, 40.18% at 2 mg/mL). As a result, Aralia elata(Miq.) Seem shoot extract was the most effective in terms of acetylcholinesterase inhibitory activity (35.94% at 1 mg/mL). In the β-secretase activity assay, all 10 kinds wild vegetables extracts showed low inhibitory activity, and Aralia elata(Miq.) Seem shoot extract had highest inhibitory activity among the 10 wild vegetables extracts was 14.99%. Taken together, these results showed that Aralia elata(Miq.) Seem shoot extract has potential cognition improvement impact, suggesting that it may provide an effective strategy for improving cognition.

Effect of 42 amino acid long amyloid-β peptides on Arabidopsis plants

  • Lee, HanGyeol;Kim, Ji Woo;Jeong, Sangyun;An, Jungeun;Kim, Young-Cheon;Ryu, Hojin;Lee, Jeong Hwan
    • Journal of Plant Biotechnology
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    • 제47권4호
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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.

봉선화 전초의 메탄올 추출물이 신경세포에서 아밀로이드 전구단백질의 대사에 미치는 영향 (Effects of MeOH Extract of Impatiens balsamina L. on the Metabolism of Amyloid Precursor Protein in Neuroblastoma Cells)

  • 조윤정;임재윤
    • 생약학회지
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    • 제46권1호
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    • pp.72-77
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    • 2015
  • One of the most common forms of dementia, Alzheimer's disease (AD) is a progressive neurodegenerative disorder symptomatically characterized by impairment in memory and cognitive abilities. AD is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}$-amyloid ($A{\beta}$) peptides, believed to be neurotoxic and now is also considered to have a role on the mechanism of memory dysfunction. In this study, we tested that MeOH extract of Impatiens balsamina L. (IBM) affects on the processing of APP from the APPswe over-expressing Neuro2a cell line. We found that IBM increased over 2 folds of the $sAPP{\alpha}$ secretion level, a main metabolite of ${\alpha}$-secretase. We shown that IBM reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ without cytotoxicity. BACE (${\beta}$-site APP cleaving enzyme) FRET assay shown that BACE activity was specifically decreased in the presence of IBM. We suggest that Impatiens balsamina L. may be an useful source to develop a herbal medicine of BACE inhibitor for Alzheimer's disease.

전통주의 항치매 활성과 심혈관질환 활성 및 항산화 활성 탐색 (Characterization of Anti-dementia, Cadiovascular and Antioxidant Functionalities in Korean Traditional Alcoholic Beverages)

  • 서동수;김재호;안병학;이종수
    • 한국미생물·생명공학회지
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    • 제36권4호
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    • pp.320-325
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    • 2008
  • 새로운 고품질의 전통주 개발을 위한 자료를 얻고자 시판 전통주들을 수집하여 이들의 물리화학적 성질과 항치매활성, 심혈관질환활성 및 노화억제활성등을 조사하였다. 수집된 45종의 전통주들의 에탄을 함량은 $7.0%{\sim}52.0%$로 다양하였고 pH는 $3.05{\sim}5.28$이었으며 SBB-ju 전통주가 비교적높은 1.37%의 총산을 함유하고 있었다. 항치매성 $\beta$-secretase 저해활성은 PMR-ju가 42.5%로 제일 높았으나 acetylcholinesterase와 butyrylcholinesterase 저해활성은 없거나 20% 미만의 낮은 활성을 보였다. 항고혈압성 ACE저해활성은 YON-ju가 85.6%로 조사한 모든 생리기능성 중 가장 우수하였으나 혈전용해활성은 없었다. 항노화성 전자공여능은 SBB-ju(A)가 72.2%을 보여 높았으나 SOD 유사활성과 혈전용해활성등은 매우 낮거나 없었다. 최종 항고혈압활성 우수 기능성 주류로 선발된 YON-ju의 주, 부원료 추출물들의 항고혈압 활성을 조사한 결과 인삼의 물과 에탄을 추출물, 멥쌀의 물추출물 및 국화의 에탄올추출물에서 항고혈압활성이 높은것으로 보아 발효중에 이들로부터 항고혈압성 ACE 저해물질이 용출되거나 이들의 분해산물들이 YON-ju의 항고혈압 활성을 상승시킨 것으로 사료 되었다.

Increase of Amyloid-Beta Peptide Generation in High Cholesterol Diet Rabbit Brain

  • Lee, Yong-Kyoung;Son, Dong-Ju;Lee, Jae-Woong;Lee, Hyung-Woo;Yun, Young-Won;Oh, Ki-Wan;Hong, Jin-Tae
    • Biomolecules & Therapeutics
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    • 제15권1호
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    • pp.34-39
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    • 2007
  • Alzheimer's disease (AD) is an abnormal accumulation of the ${\beta}$-amyloid protein $(A{\beta})$ in specific brain region. It has been speculated that disturbance in cholesterol homeostasis may contribute to the etiology of AD by increasing $A{\beta}$ generation. However, conclusive evidence and possible mechanism has not been reported. In the present study, we demonstrated that rabbits treated with 0.5% cholesterol for 16 weeks increased serum total cholesterol, triacylglycerol, and low-density lipoprotein levels. $A{\beta}$ levels is higher in the hippocampus of brain in cholesterol dieted rabbits than that of normal diet rabbis. Expression and activities of ${\beta}-$ and ${\gamma}-$ secretases, the enzymes that cleave ${\beta}$-amyloid precursor protein to generate $A{\beta}$, were also increased in hippocampus of high cholesterol dieted rabbit than those of normal dieted rabbits. Our results suggest that high cholesterol diet may be associated with increased $A{\beta}$ accumulation in the brain of rabbits, and suggest that high cholesterol diet may be causal factor in the development or progression of AD.

Structure of CT26 in the C-terminal of Amyloid Precursor Protein Studied by NMR Spectroscopy

  • Kang, Dong-Il;Baek, Dong-Ha;Shin, Song-Yub;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • 제26권8호
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    • pp.1225-1228
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    • 2005
  • C-terminal fragments of APP (APP-CTs), that contain A$\beta$ sequence, are found in neurotic plaques, neurofibrillary tangles and the cytosol of lymphoblastoid cells obtained from AD patients. CT26, Thr639-Asp664 (TVIVITLVMLKKKQYTSIHH GVVEVD) includes not only the transmembrane domain but also the cytoplasmic domain of APP. This sequence is produced from cleavage of APP by caspase and $\gamma$-secretase. In this study, the solution structure of CT26 was investigated using NMR spectroscopy and circular dichroism (CD) spectropolarimeter in various membrane-mimicking environments. According to CD spectra and the tertiary structure of CT26 determined in TFE-containing aqueous solution, CT26 has an α-helical structure from $Val^{2}\;to\;Lys^{11}$ in TFE-containing aqueous solution. However, according to CD data, CT26 adopts a $\beta$-sheet structure in the SDS micelles and DPC micelles. This result implies that CT26 may have a conformational transition between $\alpha$-helix and $\beta$-sheet structure. This study may provide an insight into the conformational basis of the pathological activity of the C-terminal fragments of APP in the model membrane.

Effects of chronic alcohol consumption on expression levels of APP and Aβ-producing enzymes

  • Kim, Sae-Rom;Jeong, Hye-Young;Yang, Sung-Hee;Choi, Sung-Pil;Seo, Min-Young;Yun, Young-Kwang;Choi, Yu-Ri;Baik, Sang-Ha;Park, Jong-Sung;Gwon, A-Ryeong;Yang, Dong-Kwon;Lee, Chan-Ho;Lee, Sun-Mee;Park, Kye-Won;Jo, Dong-Gyu
    • BMB Reports
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    • 제44권2호
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    • pp.135-139
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    • 2011
  • Chronic alcohol consumption contributes to numerous diseases, including cancers, cardiovascular diseases, and liver cirrhosis. Epidemiological studies have shown that excessive alcohol consumption is a risk factor for dementia. Along this line, Alzheimer's disease (AD) is the most common form of dementia and is caused by the accumulation of amyloid-$\beta$ ($A{\beta}$ plaques in neurons. In this study, we hypothesized that chronic ethanol consumption is associated with pathological processing of APP in AD. To investigate the relationship between chronic alcohol consumption and $A{\beta}$ production, brain samples from rats fed an alcohol liquid diet for 5 weeks were analyzed. We show that the expression levels of APP, BACE1, and immature nicastrin were increased in the cerebellum, hippocampus, and striatum of the alcohol-fed group compared to the control group. Total nicastrin and PS1 levels were induced in the hippocampus of alcohol-fed rats. These data suggest that the altered expression of APP and $A{\beta}$-producing enzymes possibly contributes to the chronic alcohol consumption-mediated pathogenesis of AD.

Hopea chinensis (Merr.) Hand.-Mazz. 메탄올 추출물이 신경세포에서 아밀로이드 전구 단백질 대사에 미치는 영향 (The Effects of MeOH Extract of Hopea chinensis (Merr.) Hand.-Mazz. on the Metabolism of Amyloid Precursor Protein in Neuroblastoma Cells)

  • 쉬레스타 아비나쉬 찬드라;김주은;함하늘;조윤정;트란 더 바이트;엄상미;임재윤
    • 생약학회지
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    • 제49권2호
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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.

Stereospecific Synthesis of the (2R,3S)- and (2R,3R)-3-Amino-2-hydroxy-4-phenylbutanoic Acids from D-Glucono-δ-lactone

  • Lee, Jin Hwan;Kim, Jin Hyo;Lee, Byong Won;Seo, Woo Duck;Yang, Min Suk;Park, Ki Hun
    • Bulletin of the Korean Chemical Society
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    • 제27권8호
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    • pp.1211-1218
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    • 2006
  • The enantiomerically pure (2R,3S)- and (2R,3R)-3-amino-2-hydroxy-4-phenylbutanoic acids (AHPBA) 1 and 3 are readily obtained from D-glucono-a-lactone. Both AHPBAs are the structural key units of KMI derivatives which are the potent inhibitors of BACE 1 ($\beta$-secretase) and HIV protease. Additionally, the obtained AHPBAs 1 and 3 are converted to dipeptides of bestatin stereoisomers 2 and 4.