• Title/Summary/Keyword: $A{\beta}$ Peptide

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Ginsenoside Rg3 enhances phagocytosis of microglia when activated by $\beta$-amyloid in rat primary culture

  • Joo, Seong-Soo;Kang, Hee-Chul;Hwang, Kwang-Woo;Lee, Do-Ik
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.136.1-136.1
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    • 2003
  • $\beta$-amyloid (A$\beta$) peptide produced from amyloid precursor protein (APP) is a major cause of Alzheimer's disease (AD). Therefore, in early phase of AD, imbalance of the production and the clearance of $A\beta$ is regarded as an important factor to progressive AD presenting senile plaque, a hallmark of AD. In the present study, we wanted to verify whether Rg3 can playa role in helping microglia engulfing $A\beta$ peptides. Validations for the study was conducted by using DiI-Ac-LDL, which attached only on type A macrophage scavenger receptor (MSR-A) and ligands for he receptor, fucoidan. (omitted)

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A Combination Strategy for Construction of Peptide-β2m-H-2Kb Single Chain with Overlap Extension PCR and One-Step Cloning

  • Xu, Tao;Li, Xiaoe;Wu, You;Shahzad, Khawar Ali;Wang, Wei;Zhang, Lei;Shen, Chuanlai
    • Journal of Microbiology and Biotechnology
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    • v.26 no.12
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    • pp.2184-2191
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    • 2016
  • The time-consuming and high-cost preparation of soluble peptide-major histocompatibility complexes (pMHC) currently limits their wide uses in monitoring antigen-specific T cells. The single-chain trimer (SCT) of peptide-${\beta}2m$-MHC class I heavy chain was developed as an alternative strategy, but its gene fusion is hindered in many cases owing to the incompatibility between the multiple restriction enzymes and the restriction endonuclease sites of plasmid vectors. In this study, overlap extension PCR and one-step cloning were adopted to overcome this restriction. The SCT gene of the $OVA_{257-264}$ peptide-$(GS_4)_3-{\beta}2m-(GS_4)_4-H-2K^b$ heavy chain was constructed and inserted into plasmid pET28a by overlap extension PCR and one-step cloning, without the requirement of restriction enzymes. The SCT protein was expressed in Escherichia coli, and then purified and refolded. The resulting $H-2K^b/OVA_{257-264}$ complex showed the correct structural conformation and capability to bind with $OVA_{257-264}$-specific T-cell receptor. The overlap extension PCR and one-step cloning ensure the construction of single-chain MHC class I molecules associated with random epitopes, and will facilitate the preparation of soluble pMHC multimers.

Identification of a Peptide Enhancing Mucosal and SystemicImmune Responses against EGFP after Oral Administration in Mice

  • Kim, Sae-Hae;Lee, Kyung-Yeol;Kim, Ju;Park, Seung-Moon;Park, Bong Kyun;Jang, Yong-Suk
    • Molecules and Cells
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    • v.21 no.2
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    • pp.244-250
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    • 2006
  • Gangliosides are receptors for various peptides and proteins including neuropeptides, ${\beta}$-amyloid proteins, and prions. Recently, the role of gangliosides in mucosal immunization has attracted attention due to the emerging interest in oral vaccination. Ganglioside GM1 exists in abundance on the surface of the M cells of Peyer's patch, a well-known mucosal immunity induction site. In the present study we identified a peptide ligand for GM1 and tested whether it played a role in immune induction. GM1-binding peptides were selected from a phage-displayed dodecapeptide library and one peptide motif, GWKERLSSWNRF, was fused to the C-terminus of enhanced green fluorescent protein (EGFP). The fusion protein, but not EGFP fused with a control peptide, was concentrated around Peyer's patch after incubation in the lumen of the intestine ex vivo. Furthermore, oral feeding of the fusion protein but not control EGFP induced mucosal and systemic immune responses against EGFP resembling Th2-type immune responses.

Searching for blue ocean of Alzheimer's disease drug discovery

  • MookJung, In-Hee
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2006.04a
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    • pp.109-120
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    • 2006
  • Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathological hallmarks of AD are senile plaques and neurofibrillary tangles in the brain. Major component of senile plaques is amyloid beta peptide(A$\beta$) which is derived from amyloid precursor protein (APP). A$\beta$ is generated through the sequential cleavage of App by $\beta$ - and $\gamma$-secretases. $\beta$-secretase excises the ectodomain of APP ($\beta$-APPs) to leave a 99-amino acid long C-terminal fragment (APP-C99-CTF) in the membrane. $\gamma$-secretase then cleaves this membrane-tethered APP-CTF within the transmembrane domain, so releasing A$\beta$ peptides and APP-intracellular domain (AICD). Thus, $\beta$- and $\gamma$-secretase are regarded to perform the key steps in the pathogenesis of AD and have become important therapeutic targets in the prevention and treatment of AD. Enormous efforts have been focused to develop the amyloid beta related drug for cure of AD becuase A$\beta$ is believed to be one of the major causes of AD. since major pharmaceutical companies in world wide base compete to develop new drug for AD, we have to be careful to choose the drug target to success the tough race. In the present talk, possible drug targets based on basic research results will be discussed. These molecules should be a good target for development of new drug for AD and be less competitive to have a good shape for world wide competition.

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Protection effect of New-Yeolda-Hanso tang against $\beta$-Amyloid Induced Cytotoxicity in NGF-differentiated PC12 Cells ($\beta$-Amyloid로 유도된 신경독성에 대한 열다한소탕(熱多寒少湯) 가감방(加感方)의 항(抗)치매효과)

  • Bae, Na-Young;Yang, Hyun-Ok;Ahn, Taek-Won
    • Journal of Sasang Constitutional Medicine
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    • v.21 no.3
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    • pp.138-153
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    • 2009
  • 1. Objectives: Yeolda-Hanso tang (YH) has long been used as traditional herbal formula in Korea as various diseases. Now we modified Yeolda-Hanso tang (YH) for neurodegenerative diseases treatment and named New-Yeolda-Hanso tang (NYH). We investigated neuroprotective effects of NYH on NGF-differentiated PC12 cells cytotoxicity induced by $\beta$-Amyloid peptide (A$\beta$25-35) and evaluated the ability of NYH to prevent and treat for neurodegenerative diseases via autophagy enhancement. 2. Methods and Results: 1) Protective effect of NYH on PC12 cells cytotoxity induced by A$\beta$25-35. PC12 cells survival was measured by MTT and lactate dehydrogenase (LDH) assay. $20{\mu}M$ $\beta$-Amyloid peptide (A$\beta$25-35) induced cytotoxicity on NGF-differentiated PC12 cells. NYH attenuated the cytotoxic effects of A$\beta$25-35 in a dose-dependent manner. 2) Pharmacological induction of Autophagy by NYH in PC12 cells Autophagy induction and activation was measured by immunoblot assay. Marker of autophagy, LC3 II expression and the ratio of LC3-II/I was slightly increased in the protein treated with YH, and significantly augmented in the protein treated with NYH. NYH-induced increase of LC3-II protein level was inhibited by 3MA. 3) Induction of Autophagy by NYH on A$\beta$25-35-induced injury in PC12 cells In MTT assay, $100{\mu}g/ml$ re-treated NYH attenuated $20{\mu}M$ A$\beta$25-35-induced cytotoxicity in PC12 cells. Protection effect of NYH was blocked by autophagy inhibitor 3MA. In immunoblot assay, $1200{\mu}g/ml$ pre-treated NYH activated autophagy in $20{\mu}M$ A$\beta$25-35-induced cytotoxicity in PC12 cells. The observed effect was partially blocked by 3MA. 3. Conclusions: All the results indicated that NYH possesses neuroprotective potential partially mediated by autophagy enhancement and NYH may be considered to be a promising new herbal formula to prevent and treat for neurodegenerative diseases including Alzheimer's disease (AD).

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Expression Profiles of Kiss2, GPR54 and GnRH Receptor I mRNAs in the Early Life Stage of Nile Tilapia, $Oreochromis$ $niloticus$

  • Park, Jin-Woo;Kim, Jung-Hyun;Jin, Ye-Hwa;Kwon, Joon-Yeong
    • Development and Reproduction
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    • v.16 no.1
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    • pp.31-38
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    • 2012
  • Kisspeptin has been implicated in the process of puberty onset in various animal groups. This peptide is encoded by a gene, Kiss1 in avian and mammalian species. Contrary to these higher vertebrates, however, fish appeared to have another gene, Kiss2 that also codes for the precursor peptide of kisspeptin. To figure out biological significance of this gene during the puberty onset in fish, the expression profile of Kiss2 gene was investigated in the brain of Nile tilapia together with genes of GPR54, GnRH receptorI (rGnRHI) and GTH subunits ($LH{\beta}$ and $FSH{\beta}$). Expression of Kiss2 mRNA significantly increased at 2 weeks post hatch (wph) and 13 wph ($P$<0.05). This increase coincided with the increases of GPR54 and rGnRH I gene expression. Detection of $LH{\beta}$ and $FSH{\beta}$ subunit gene expression was possible later than 13 wph, indicating the activation of gonadotrophs in the pituitary. Data obtained from this study strongly suggest that, in addition to Kiss1 gene, Kiss2 gene is deeply associated with the onset of puberty by the activation of hypothalamus pituitary gonadal axis in Nile tilapia.

Study on pathology of Alzheimer's disease, trends and future strategy for research (치매의 병리(病理), 연구동향(硏究動向)과 향후(向後) 연구전략(硏究戰略)에 대(對)한 고찰(考察))

  • Oh, Young-Sun;Kim, Sung-Hoon
    • 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.

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Structure-Function of the TNF Receptor-like Cysteine-rich Domain of Osteoprotegerin

  • Shin, Joon;Kim, Young-Mee;Li, Song-Zhe;Lim, Sung-Kil;Lee, Weontae
    • Molecules and Cells
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    • v.25 no.3
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    • pp.352-357
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    • 2008
  • Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits osteoclastogenesis and is closely associated with bone resorption processes. We have designed and determined the solution structures of potent OPG analogue peptides, derived from sequences of the cysteine-rich domain of OPG. The inhibitory effects of the peptides on osteoclastogenesis are dose-dependent ($10^{-6}M-10^{-4}M$), and the activity of the linear peptide at $10^{-4}M$ is ten-fold higher than that of the cyclic OPG peptide. Both linear and cyclic peptides have a ${\beta}$-turn-like conformation and the cyclic peptide has a rigid conformation, suggesting that structural flexibility is an important factor for receptor binding. Based on structural and biochemical information about RANKL and the OPG peptides, we suggest that complex formation between the peptide and RANKL is mediated by both hydrophobic and hydrogen bonding interactions. These results provide structural insights that should aid in the design of peptidyl-mimetic inhibitors for treating metabolic bone diseases caused by abnormal osteoclast recruitment.

Effect of Agarase Signal Peptide from Agarivorans albus YKW-34 on Protein Secretion in Escherichia coli (대장균에서 단백질 분비에 대한 Agarivorans albus YKW-34의 Agarase 시그널펩티드의 효과)

  • Lee, Joo-Young;Song, Dae-Geun;Son, Jin-Ki;Pan, Cheol-Ho
    • Journal of Applied Biological Chemistry
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    • v.53 no.2
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    • pp.105-107
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    • 2010
  • To overcome the limitation of E. coli expression system such as inclusion body formation and disulfide bond failure, we tried to express the heterologous protein as a secreted form. We adopted agarase signal peptide (ASP; 23 amino acid residues) from Agarivorans albus YKW-34 which is one of marine bacteia. When we used ASP to express $\beta$-agarase, about 42% activity was detected in media.

Moderate diet-induced weight loss is associated with improved insulin sensitivity in middle-aged healthy obese Korean women

  • Lee, Hye-Ok;Yim, Jung-Eun;Kim, Young-Seol;Choue, Ryowon
    • Nutrition Research and Practice
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    • v.8 no.4
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    • pp.469-475
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    • 2014
  • BACKGROUND/OBJECTIVE: The goal of the present study was to investigate the effects of moderate caloric restriction on ${\beta}$-cell function and insulin sensitivity in middle-aged obese Korean women. SUBJECTS/METHODS: Fifty-seven obese pre-menopausal Korean women participated in a 12-week calorie restriction program. Data on total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and fasting serum levels of glucose, insulin, C-peptide, blood pressure, leptin and anthropometrics were collected. A dietary intake assessment was based on three days of food recording. Additionally, ${\beta}$-cell function [homeostasis model assessment of ${\beta}$-cell (HOMA-${\beta}$), insulinogenic index (ISI), C-peptide:glucose ratio, and area under curve insulin/glucose ($AUC_{ins/glu}$)] and insulin sensitivity [homeostasis model assessment for insulin resistance (HOMA-IR), Quantitative insulin-sensitivity check index (QUICKI) and Matsuda index (MI)] were recorded. RESULTS: When calories were reduced by an average of 422 kcal/day for 12 weeks, BMI (-2.7%), body fat mass (-10.2%), and waist circumference (-5%) all decreased significantly (P < 0.05). After calorie restriction, weight, body fat percentage, hip circumference, BP, TC, HDL-C, LDL-C, plasma glucose at fasting, insulin at fasting and 120 min, $AUC_{glu}$ and the insulin area under the curve all decreased significantly (all P < 0.05), while insulin sensitivity (HOMA-IR, QUICKI and Matsuda index) measured by OGTT improved significantly (P < 0.01). CONCLUSIONS: Moderate weight loss due to caloric restriction with reduction in insulin resistance improves glucose tolerance and insulin sensitivity in middle-aged obese women and thereby may help prevent the development of type 2 diabetes mellitus.